MedWorm.com provides a medical RSS filtering service. Over 6000 RSS medical sources are combined and output via different filters. This feed contains the latest items from the 'CNS and Neurological Disorders Drug Targets' source. Sun, 21 Mar 2010 14:57:31 +0100 http://www.medworm.com/index.php?rid=3349755&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20205647%26dopt%3DAbstract Authors: Szekely CA, Zandi PP Alzheimer's disease imposes a significant public health burden that will only worsen as the population ages. Thus, there is considerable motivation to develop effective strategies to treat, or more ideally, prevent the disease. Epidemiologic evidence has suggested that non-steroidal anti-inflammatory drugs (or NSAIDs) may be neuro-protective. However, this evidence is controversial. Observational studies in humans have found that the use of NSAIDs is associated with a lower risk of developing Alzheimer's disease. By contrast, randomized trials have reported that NSAIDs are not effective in treating patients with clinically established disease nor in preventing the onset of dementia among those who are cognitively normal or have mild cognitive impairment. I... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=3349755 Sat, 06 Mar 2010 00:00:00 +0100 3349755 http://www.medworm.com/index.php?rid=3349754&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20205648%26dopt%3DAbstract Authors: Town T Few topics in the field of Alzheimer's disease (AD) research have brought about the level of excitement and interest as the role of inflammation and immunity in the pathobiology and treatment of the disease. In this special issue of the journal, experts in the field give their views on how inflammatory processes and the immune system intersect- at both etiological and treatment levels- with disease biology. Collectively, nearly three decades of work are covered in this special issue, beginning with the first epidemiologic studies that showed an inverse risk relationship between AD and use of non-steroidal anti-inflammatory drugs, and ending with "immunotherapy" approaches and recent studies examining the roles of innate immune cells including microglia and peripheral mo... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=3349754 Sat, 06 Mar 2010 00:00:00 +0100 3349754 http://www.medworm.com/index.php?rid=3349763&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20205639%26dopt%3DAbstract Authors: Cribbs DH Pre-clinical and clinical data suggest that the development of a safe and effective anti-amyloid-beta (Abeta) immunotherapy for Alzheimer's disease (AD) will require therapeutic levels of anti-Abeta antibodies, while avoiding proinflammatory adjuvants and autoreactive T cells which may increase the incidence of adverse events in the elderly population targeted to receive immunotherapy. The first active immunization clinical trial with AN1792 in AD patients was halted when a subset of patients developed meningoencephalitis. The first passive immunotherapy trial with bapineuzumab, a humanized monoclonal antibody against the end terminus of Abeta, also encountered some dose dependent adverse events during the Phase II portion of the study, vasogenic edema in 12 cases, w... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=3349763 Fri, 05 Mar 2010 00:00:00 +0100 3349763 http://www.medworm.com/index.php?rid=3349762&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20205640%26dopt%3DAbstract Authors: Fu HJ, Liu B, Frost JL, Lemere CA Alzheimer's disease (AD) is a progressive, degenerative disorder of the brain and the most common form of dementia among the elderly. As the population grows and lifespan is extended, the number of AD patients will continue to rise. Current clinical therapies for AD provide partial symptomatic benefits for some patients; however, none of them modify disease progression. Amyloid-beta (Abeta peptide, the major component of senile plaques in AD patients, is considered to play a crucial role in the pathogenesis of AD thereby leading to Abeta as a target for treatment. Abeta immunotherapy has been shown to induce a marked reduction in amyloid burden and an improvement in cognitive function in animal models. Although preclinical studies were success... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=3349762 Fri, 05 Mar 2010 00:00:00 +0100 3349762 http://www.medworm.com/index.php?rid=3349761&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20205641%26dopt%3DAbstract Authors: Fiala M Morbidities of aging and Alzheimer's disease (AD) have been related to defective functions of both T cells and macrophages leading to brain amyloidosis and inflammation. In AD patients, "inflammaging" may be associated with an increase of incompetent memory T cells and inflammatory cytokines produced by macrophages, whereas defective clearance of amyloid-beta 1-42 (Abeta) may be related to defective transcription of immune genes necessary for Abeta phagocytosis, beta-1,4-mannosyl-glycoprotein 4-beta-N-acetylglucosaminyltransferase and Toll-like receptors. However, AD shows considerable heterogeneity of disease manifestations and mechanisms. The approaches to re-balancing Abeta immunity and inflammation are being pursued in transgenic animal models and peripheral blood ... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=3349761 Fri, 05 Mar 2010 00:00:00 +0100 3349761 http://www.medworm.com/index.php?rid=3349760&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20205642%26dopt%3DAbstract Authors: Colton M, Wilcock DM Since the original identification of microglia as a principal player in the brain's innate immune response, microglial activation has been widely studied. Recent studies suggest that microglial responses are heterogeneous, requiring a more precise definition of the functional outcomes of their participation in disease. Similarly to other tissue macrophages, microglia respond to inflammatory or injurious stimuli in the CNS in a pre-programmed manner that is designed to both kill and to set the stage for repair and resolution of the disease. In vitro studies on acute immune responses have provided key information on the initiation, signaling pathways and products of activated macrophages. However, in chronic neurodegenerative diseases such as Alzheimer's dis... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=3349760 Fri, 05 Mar 2010 00:00:00 +0100 3349760 http://www.medworm.com/index.php?rid=3349759&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20205643%26dopt%3DAbstract Authors: Hickman SE, El Khoury J Alzheimer's disease (AD) is associated with a significant neuroinflammatory component. Mononuclear phagocytes including monocytes and microglia are the principal cells involved, and they accumulate at perivascular sites of beta-amyloid (Abeta) deposition and in senile plaques. Recent evidence suggests that mononuclear phagocyte accumulation in the AD brain is dependent on chemokines. CCL2, a major monocyte chemokine, is upregulated in the AD brain. Interaction of CCL2 with its receptor CCR2 regulates mononuclear phagocyte accumulation in a mouse model of AD. CCR2 deficiency leads to lower mononuclear phagocyte accumulation and is associated with higher brain Abeta levels, specifically around blood vessels, suggesting that monocytes accumulate at sites o... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=3349759 Fri, 05 Mar 2010 00:00:00 +0100 3349759 http://www.medworm.com/index.php?rid=3349758&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20205644%26dopt%3DAbstract Authors: Mandrekar S, Landreth GE One hundred and fifty years have elapsed since the original discovery of the microglial cell by Virchow. While this cell type has been well studied, the role of microglia in the pathology of many central nervous system diseases still remains enigmatic. It is widely accepted that microglial-mediated inflammation contributes to the progression of Alzheimer's disease (AD); however, the precise mechanisms through which these cells contribute to AD-related inflammation remains to be elucidated. In the AD brain, microglial cells are found in close association with amyloid beta (Abeta) deposits. Histological examination of AD brains as well as cell culture studies have shown that the interaction of microglia with fibrillar Abeta leads to their phenotypic acti... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=3349758 Fri, 05 Mar 2010 00:00:00 +0100 3349758 http://www.medworm.com/index.php?rid=3349757&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20205645%26dopt%3DAbstract Authors: Giunta B, Rezai-Zadeh K, Tan J As the number of elderly individuals rises, Alzheimer's disease (AD), marked by amyloid-beta deposition, neurofibrillary tangle formation, and low-level neuroinflammation, is expected to lead to an ever-worsening socioeconomic burden. AD pathoetiologic mechanisms are believed to involve chronic microglial activation. This phenomenon is associated with increased expression of membrane-bound CD40 with its cognate ligand, CD40 ligand (CD40L), as well as increased circulating levels of soluble forms of CD40 (sCD40) and CD40L (sCD40L). Here, we review the role of this inflammatory dyad in the pathogenesis of AD. In addition, we examine potential therapeutic strategies such as statins, flavonoids, and human umbilical cord blood transplantation, all of ... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=3349757 Fri, 05 Mar 2010 00:00:00 +0100 3349757 http://www.medworm.com/index.php?rid=3349756&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20205646%26dopt%3DAbstract Authors: Fiala M, Frautschy SA Alzheimer disease (AD) is accompanied by an activation of the innate immune system, and many epidemiological studies have shown reduced risk for dementia or AD associated with chronic consumption of non-steroidal anti-inflammatory drugs (NSAIDS). These observations led to animal model studies to test the hypothesis that NSAIDs can be disease-modifying for some aspects of AD pathogenesis. NSAIDS cannot only suppress inflammatory targets, which could contribute to neuroprotection, they also slow amyloid deposition by mechanisms that remain unclear. Several large clinical trials with NSAID therapies with AD patients have failed and cyclooxygenase-2 does not appear to be a useful target for disease modifying therapy. However, there may be apolipoprotein E E4 ... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=3349756 Fri, 05 Mar 2010 00:00:00 +0100 3349756 http://www.medworm.com/index.php?rid=3338734&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20201810%26dopt%3DAbstract This article will review the major clinical trials of disulfiram spanning nearly 60 years. We will discuss the pharmacodynamics and pharmacokinetics of disulfiram, indications and limitations of its use, suggestions for appropriate patient populations, and monitoring for compliance and adverse effects. We will also review recent literature on newer potential applications for disulfiram use via its unique action on dopamine beta-hydroxylase. PMID: 20201810 [PubMed - in process] (Source: CNS and Neurological Disorders Drug Targets) CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=3338734 Mon, 01 Mar 2010 00:00:00 +0100 3338734 http://www.medworm.com/index.php?rid=3338733&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20201811%26dopt%3DAbstract Authors: Ray LA, Chin PF, Miotto K Naltrexone is an opioid receptor antagonist with established efficacy, albeit moderate, for the treatment of alcohol dependence. This manuscript provides a critical review of the literature on naltrexone as a pharmacotherapy for alcoholism by covering the following areas: (a) clinical findings from treatment studies; (b) pharmacokinetics and safety data; (c) medication compliance and persistence; and (d) neurobiological and biobehavioral mechanisms of action of naltrexone for the indication of alcohol dependence. This review will then focus on the emerging literature on naltrexone pharmacogenetics, which has the potential to identify responders on the basis of genetic variation and to use genetic tools to individualize the use of this medication. Limi... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=3338733 Mon, 01 Mar 2010 00:00:00 +0100 3338733 http://www.medworm.com/index.php?rid=3338732&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20201812%26dopt%3DAbstract Authors: Mason BJ, Heyser CJ Alcoholism is one of the most prevalent substance dependence disorders in the world. Advances in research in the neurobiological mechanisms underlying alcohol dependence have identified specific neurotransmitter targets for the development of pharmacological treatments. Acamprosate, marketed under the brand name Campral, is an orally administered drug available by prescription in the U.S. and throughout much of the world for treating alcohol dependence. Its safety and efficacy have been demonstrated in numerous clinical trials worldwide. Here we provide an overview of acamprosate in the context of the neurobiological underpinnings of alcohol dependence. We propose that unlike previously available pharmacotherapies, acamprosate represents a prototypical neur... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=3338732 Mon, 01 Mar 2010 00:00:00 +0100 3338732 http://www.medworm.com/index.php?rid=3338731&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20201813%26dopt%3DAbstract Authors: Leggio L, Garbutt JC, Addolorato G Both preclinical and clinical research studies have shown the GABA(B) receptor agonist baclofen represents a promising treatment for alcohol dependence. Preliminary clinical studies indicate that baclofen is able to suppress withdrawal symptoms in alcohol-dependent patients affected by the alcohol withdrawal syndrome. Moreover, baclofen has shown efficacy and safety in promoting alcohol abstinence in alcohol dependent patients in two placebo-controlled trials including one in alcohol-dependent patients with liver cirrhosis. These trials also demonstrated that baclofen was associated with reductions in withdrawal-related anxiety and alcohol craving. However, more work is needed to clearly demonstrate the efficacy of baclofen and to ascertain w... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=3338731 Mon, 01 Mar 2010 00:00:00 +0100 3338731 http://www.medworm.com/index.php?rid=3338730&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20201814%26dopt%3DAbstract Authors: De Sousa A Alcohol dependence is a major health problem worldwide. Various pharmacological agents have been used in the management of alcohol dependence. This review looks at the role of topiramate and other anticonvulsants in the management of alcohol dependence. Topiramate is the most widely used anticonvulsant in the treatment of alcohol dependence. The literature on topiramate is reviewed and critically analyzed, along with its proposed mechanism of action in alcohol dependence. A review of data available on other anticonvulsants like carbamazepine, oxcarbazepine, sodium valproate, gabapentin and levetiracetam are presented and their potential in the treatment of alcohol dependence is considered, together with future research directions. PMID: 20201814 [PubMed - in pro... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=3338730 Mon, 01 Mar 2010 00:00:00 +0100 3338730 http://www.medworm.com/index.php?rid=3338729&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20201815%26dopt%3DAbstract This article proposes a potential role for aripiprazole in alcoholism treatment, and suggests that more randomized controlled trials should be designed at appropriate doses to better understand aripiprazole's potential role as a treatment option. More options are needed to treat alcoholics that fall into different subgroups (e.g., those with impulsive disorders), or non-responsive to available treatments. Early results with aripiprazole are promising and warrant further exploration. PMID: 20201815 [PubMed - in process] (Source: CNS and Neurological Disorders Drug Targets) CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=3338729 Mon, 01 Mar 2010 00:00:00 +0100 3338729 http://www.medworm.com/index.php?rid=3338728&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20201816%26dopt%3DAbstract Authors: Maccioni P, Colombo G, Carai MA The present paper summarizes the results of a number of pharmacological studies implicating the cannabinoid CB(1) receptor in the neural circuitry regulating different alcohol-related behaviors in rodents. Specifically, cannabinoid CB(1) receptor antagonists - including the prototype, rimonabant - have been reported to suppress: (a) acquisition and maintenance of alcohol drinking behavior under the 2-bottle "alcohol vs water" choice regimen; (b) the increase in alcohol intake occurring after a period of alcohol abstinence (an experimental model of alcohol relapse); (c) alcohol's reinforcing and motivational properties measured in rats trained to perform a specific task (e.g., lever-pressing) to access alcohol; (d) reinstatement of extinguished a... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=3338728 Mon, 01 Mar 2010 00:00:00 +0100 3338728 http://www.medworm.com/index.php?rid=3338727&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20201817%26dopt%3DAbstract Authors: Chatterjee S, Bartlett SE Alcohol use disorders (AUDs) are complex, and developing effective treatments will require the combination of novel medications and cognitive behavioral therapy approaches. Epidemiological studies have shown there is a high correlation between alcohol consumption and tobacco use, and the prevalence of smoking in alcoholics is as high as 80% compared to about 30% for the general population. Both preclinical and clinical data provide evidence that nicotine administration increases alcohol intake and non-specific nicotinic receptor antagonists reduce alcohol-mediated behaviors. As nicotine interacts specifically with the neuronal nicotinic acetylcholine receptor (nAChR) system, this suggests that nAChRs play an important role in the behavioral effects of... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=3338727 Mon, 01 Mar 2010 00:00:00 +0100 3338727 http://www.medworm.com/index.php?rid=3338726&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20201818%26dopt%3DAbstract Authors: Lowery EG, Thiele TE Alcoholism is a chronic disorder characterized by cycling periods of excessive ethanol consumption, withdrawal, abstinence and relapse, which is associated with progressive changes in central corticotropin-releasing factor (CRF) receptor signaling. CRF and urocortin peptides act by binding to the CRF type 1 (CRF1R) or the CRF type 2 (CRF2R) receptors, both of which have been implicated in the regulation of neurobiological responses to ethanol. The current review provides a comprehensive overview of preclinical evidence from studies involving rodents that when viewed together, suggest a promising role for CRFR antagonists in the treatment of alcohol abuse disorders. CRFR antagonists protect against excessive ethanol intake resulting from ethanol dependence ... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=3338726 Mon, 01 Mar 2010 00:00:00 +0100 3338726 http://www.medworm.com/index.php?rid=3338725&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20201819%26dopt%3DAbstract Authors: Murphy NP Nociceptin (known also as orphanin FQ) is the most recently discovered member of the endogenous opioid peptide family, albeit nearly 15 years ago. Nociceptin renders or influences many behavioral, psychological and neurobiological processes, including memory, anxiety, stress and reward. Since its discovery, results of a steady stream of studies have suggested that endogenous nociceptin might be involved in responses to addictive drugs, and that targeting the nociceptin system may be beneficial in treating addictions. The current review summarizes and critically appraises those studies, particularly those that point to an application in treating alcoholism. Overall, most, studies suggest that the endogenous nociceptin system has a physiological role in mediating or re... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=3338725 Mon, 01 Mar 2010 00:00:00 +0100 3338725 http://www.medworm.com/index.php?rid=3338724&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20201820%26dopt%3DAbstract Authors: Selvaraj S, Sun Y, Singh BB Calcium is an essential intracellular messenger and serves critical cellular functions in both excitable and non-excitable cells. Most of the physiological functions in these cells are uniquely regulated by changes in cytosolic Ca(2+) levels ([Ca(2+)](i)), which are achieved via various mechanisms. One of these mechanism(s) is activated by the release of Ca(2+) from the endoplasmic reticulum (ER), followed by Ca(2+) influx across the plasma membrane (PM). Activation of PM Ca(2+) channel is essential for not only refilling of the ER Ca(2+) stores, but is also critical for maintaining [Ca(2+)](i) that regulates biological functions, such as neurosecretion, sensation, long term potentiation, synaptic plasticity, gene regulation, as well as cellular gro... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=3338724 Mon, 01 Mar 2010 00:00:00 +0100 3338724 http://www.medworm.com/index.php?rid=3338723&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20201821%26dopt%3DAbstract Authors: Arduíno DM, Esteves AR, Oliveira CR, Cardoso SM Mitochondrial metabolism is a highly orchestrated phenomenon in which many enzyme systems cooperate in a variety of pathways to dictate cellular fate. As well as its vital role in cellular energy metabolism (ATP production), mitochondria are powerful organelles that regulate reactive oxygen species production, NAD(+)/NADH ratio and programmed cell death. In addition, mitochondrial abnormalities have been well recognized to contribute to degenerative diseases, like Parkinson's disease (PD). Particularly a deficiency in the mitochondrial respiratory chain complex I and cristae disruption have been consistently described in PD. Moreover, the products of PD-familial genes, including alpha-synuclein, Parkin, PINK1, DJ-1, LRRK2 an... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=3338723 Mon, 01 Mar 2010 00:00:00 +0100 3338723 http://www.medworm.com/index.php?rid=3338722&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20201822%26dopt%3DAbstract Authors: Burgess S, Echeverria V The active form of the serine/threonine kinase cRaf-1 is upregulated postmortem in the brains of Alzheimer's disease (AD) patients and in transgenic mouse models of AD pathology. The persistent activation of cRaf-1 can activate the proinflammatory factor NFkappaB and consequently, upregulate the expression of several of its downstream factors such as the amyloid precursor protein (APP), Cox-2 and iNOS. These factors have been found upregulated in numerous neurodegenerative conditions including AD, epilepsy, brain trauma, and psychological stress. The Raf kinase inhibitors, GW5074 and ZM336372, are neuroprotective against many different neurotoxic insults in vitro, including the Abeta peptide, glutamate and glutathione depletion. Recently, we have report... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=3338722 Mon, 01 Mar 2010 00:00:00 +0100 3338722 http://www.medworm.com/index.php?rid=3059924&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19957394%26dopt%3DAbstract Authors: Puffenbarger RA PMID: 19957394 [PubMed - in process] (Source: CNS and Neurological Disorders Drug Targets) CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=3059924 Tue, 01 Dec 2009 00:00:00 +0100 3059924 http://www.medworm.com/index.php?rid=2738420&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19702564%26dopt%3DAbstract Authors: Moreira PI, Cardoso SM, Pereira CM, Santos MS, Oliveira CR Due to the increasing number of data demonstrating a connection between diabetes and Alzheimer's disease (AD), efforts have been developed to elucidate the exact mechanism(s) underlying this connection. Although both disorders possess several overlapping features, mitochondrial dysfunction is one of the most relevant rendering mitochondria an important target of scientific research. This review discusses clinical and biochemical features shared by AD and diabetes, giving special attention to the involvement of mitochondria. The realization that mitochondria are at the intersection of cells' life and death has made them a promising target for drug discovery and therapeutic interventions. Here we also discuss in vitro, i... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=2738420 Thu, 27 Aug 2009 22:10:33 +0100 2738420 http://www.medworm.com/index.php?rid=2738419&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19702565%26dopt%3DAbstract Authors: Johnson KA, Conn PJ, Niswender CM Parkinson's disease (PD) is a neurodegenerative disorder characterized by motor symptoms including tremor and bradykinesia. The primary pathophysiology underlying PD is the degeneration of dopaminergic neurons of the substantia nigra pars compacta. Loss of these neurons causes pathological changes in neurotransmission in the basal ganglia motor circuit. The ability of ionotropic and metabotropic glutamate receptors to modulate neurotransmission throughout the basal ganglia suggests that these receptors may be targets for reversing the effects of altered neurotransmission in PD. Studies in animal models suggest that modulating the activity of these receptors may alleviate the primary motor symptoms of PD as well as side effects induced by dopam... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=2738419 Thu, 27 Aug 2009 22:10:31 +0100 2738419 http://www.medworm.com/index.php?rid=2738418&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19702566%26dopt%3DAbstract Authors: Hashimoto K In the past decade there has been increasing interest in the potential benefit of early pharmacological intervention in schizophrenia. Patients with schizophrenia show nonpsychotic and nonspecific prodromal symptoms (e.g., depression and cognitive deficits) for several years preceding the onset of frank psychosis. Several studies have demonstrated that medication with atypical antipsychotic drugs in people with prodromal symptoms may reduce the risk of subsequent transition to schizophrenia. Furthermore, a naturalistic treatment study in young people with prodromal symptoms demonstrated that medication with antidepressants could prevent the development of psychosis. Although the sample in this study was small, the results were striking. In contrast, some antidepres... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=2738418 Thu, 27 Aug 2009 22:10:29 +0100 2738418 http://www.medworm.com/index.php?rid=2738417&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19702567%26dopt%3DAbstract Authors: de Franciscis V, Esposito CL, Catuogno S, Cellai L, Cerchia L Aptamers are short non-naturally occurring single stranded DNA or RNA able to bind tightly, due to their specific three-dimensional shapes, to a multitude of targets ranging from small chemical compounds to cells and tissues. Since their first discovery, aptamers became a valuable research tool and showed great application prospected in the fundamental research, drug selection and clinical diagnosis and therapy. Thanks to their unique characteristics (low size, good affinity for the target, no immunogeneicity, chemical structures that can be easily modified to improve their in vivo applications), aptamers may represent a valid alternative to antibodies particularly for the treatment of neurological disorders that ur... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=2738417 Thu, 27 Aug 2009 22:10:26 +0100 2738417 http://www.medworm.com/index.php?rid=2738416&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19702568%26dopt%3DAbstract Authors: Nagai S, Takahashi T, Kurokawa M Acute promyelocytic leukemia (APL) is a distinct subset of acute myeloid leukemia characterized by an abnormal fusion protein, PML/RARA. All-trans retinoic acid (ATRA) and arsenic trioxide, which are the major molecularly targeted therapies in APL, affect or degrade the PML/RARA fusion protein and cause differentiation and apoptosis of APL cells. These therapies have improved the prognosis of APL patients and are now the main therapeutic options in APL. In addition, gemtuzumab ozogamicin is another targeted therapy in APL. On the other hand, the prognosis of patients with central nervous system (CNS) relapses of APL remains poor. Therefore, CNS relapses have become major concerns, and effective therapeutic approaches for CNS relapses are needed... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=2738416 Thu, 27 Aug 2009 22:10:24 +0100 2738416 http://www.medworm.com/index.php?rid=2738415&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19702569%26dopt%3DAbstract Authors: Imashuku S Diabetes insipidus and neurodegenerative disease are the two major CNS complications of Langerhans cell histiocytosis (LCH). Once it has developed, diabetes insipidus is permanent, while the outcome of neurodegenerative disease is dismal. The development of these CNS-LCH complications is closely correlated with "CNS-risk" organ involvement, namely, the presence at diagnosis of LCH lesions in cranio-facial areas. Based on recent data showing the beneficial effects of intravenous immunoglobulin (IVIG) treatment on inflammatory diseases of the central nervous system (CNS), we are currently testing whether monthly IVIG treatment (0.4 g/kg/dose) can alleviate the progression of neurodegenerative disease in LCH patients. We also hypothesize that the incidence of CNS compl... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=2738415 Thu, 27 Aug 2009 22:10:21 +0100 2738415 http://www.medworm.com/index.php?rid=2738414&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19702570%26dopt%3DAbstract Authors: Brown P Efforts to treat transmissible spongiform encephalopathy (TSE) date back to the middle of the 20(th) century. Early studies were colored by the belief that TSE was caused by a 'slow' or 'unconventional' virus, and a variety of anti-infective agents, together with scores of drugs drawn at random from other categories, predictably failed to provide any benefit, apart from polyanionic compounds and polyene antibiotics that prolonged the incubation period of disease in experimental animals. With the discovery in the 1980's that TSE apparently results from the malformation of a normal host protein, attempts at treatment could at last be rationally focused, and can be broadly categorized as genetic, immunologic, and pharmacologic. Genetic 'neutralization' of the pathogen has... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=2738414 Thu, 27 Aug 2009 22:10:19 +0100 2738414 http://www.medworm.com/index.php?rid=2738413&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19702571%26dopt%3DAbstract Authors: Riemer C, Gültner S, Heise I, Holtkamp N, Baier M Prion infections of the central nervous system (CNS) are characterized by a reactive gliosis and the subsequent degeneration of neuronal tissue. The activation of glial cells, which precedes neuronal death, is likely to be initially caused by the deposition of misfolded, in part proteinase K-resistant, isoforms (termed PrP(TSE)) of the normal cellular prion protein (PrP(c)) in the brain. Proinflammatory cytokines and chemokines released by PrP(TSE)-activated glial cells and stressed neurons may contribute directly or indirectly to the disease development by enhancement and generalization of the gliosis and via cytotoxicity for neurons. Recent studies have illustrated that interfering with inflammatory responses may represe... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=2738413 Thu, 27 Aug 2009 22:10:17 +0100 2738413 http://www.medworm.com/index.php?rid=2738412&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19702572%26dopt%3DAbstract Authors: Kranitz FJ, Simpson DM Creutzfeldt-Jakob disease (CJD) is a rare, degenerative and fatal brain disease that appears to be caused by an abnormal form of a protein called a prion. Due to the lack of an effective treatment for CJD, support for patients and family members is crucial. Appropriate education of the healthcare community on this rare disease and provision of palliative care are critically needed. The CJD Foundation and CJD Insight were formed to provide services to patients and families affected by prion diseases. PMID: 19702572 [PubMed - as supplied by publisher] (Source: CNS and Neurological Disorders Drug Targets) CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=2738412 Thu, 27 Aug 2009 22:10:14 +0100 2738412 http://www.medworm.com/index.php?rid=2738411&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19702573%26dopt%3DAbstract Authors: Morales R, Green KM, Soto C Protein Misfolding Disorders (PMDs) are a group of diseases characterized by the accumulation of abnormally folded proteins. Despite the wide range of proteins and tissues involved, PMDs share similar molecular and pathogenic mechanisms. Several epidemiological, clinical and experimental reports have described the co-existence of PMDs, suggesting a possible cross-talk between them. A better knowledge of the molecular basis of PMDs could have important implications for understanding the mechanism by which the diseases appear and progress and ultimately to develop novel strategies for treatment. Due to their similar molecular mechanisms, common therapeutic strategies could be applied for the diseases in this group. PMID: 19702573 [PubMed - as supp... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=2738411 Thu, 27 Aug 2009 22:10:12 +0100 2738411 http://www.medworm.com/index.php?rid=2738410&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19702574%26dopt%3DAbstract Authors: Supattapone S, Piro JR, Rees JR Among the candidate anti-prion chemotherapeutic agents identified to date, complex polyamines constitute the only class of compounds that possess the ability to remove pre-existing PrP(Sc) molecules from infected cells. The potency of branched polyamines such as cationic dendrimers increases with the density of positive charges on their surface. Cationic dendrimers appear to accumulate together with PrP(Sc) molecules in lysosomes, where the acidic environment facilitates dendrimer-mediated PrP(Sc) disaggregation. Dendrimers can disaggregate a range of different amyloid proteins by interacting with specific epitopes on each protein. Studies with model peptides suggest that dendrimers may cause fiber breakage and capping of elongating fibers. Pote... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=2738410 Thu, 27 Aug 2009 22:10:10 +0100 2738410 http://www.medworm.com/index.php?rid=2738409&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19702575%26dopt%3DAbstract Authors: Appleby BS Prion diseases are rare, rapidly progressive, fatal neurodegenerative illnesses caused by an abnormal isoform of the native prion protein. Creutzfeldt-Jakob disease (CJD) is the most prevalent human prion disease with three possible etiologies: sporadic, genetic, and acquired. Although acquired forms of prion disease have received the most attention, most cases are sporadic or genetic and are thus unpreventable. There is some literature on neurotransmitter system dysregulation in animal and human models of prion diseases. Several studies indicate that there is a disproportional amount of serotonin dysregulation in prion diseases and that prion-mediated cytotoxicity may be blocked by N-methyl D-aspartate (NMDA) receptor antagonists. Prion disease therapeutic investig... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=2738409 Thu, 27 Aug 2009 22:10:07 +0100 2738409 http://www.medworm.com/index.php?rid=2738408&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19702576%26dopt%3DAbstract Authors: White MD, Mallucci GR Effective treatment of neurodegenerative disease is one of the major challenges facing biomedical research. These disorders, which include Alzheimer's, Huntington's and Parkinson's diseases - as well as the rarer prion diseases - constitute an ever-increasing burden in the developed world, socially, medically and economically. The key barrier to effective therapy is that they present clinically when neuronal loss is advanced, and irreversible. Current treatments are almost all directed at modifying symptoms; few address underlying pathogenic mechanisms and are inevitably delivered too late to rescue dying neurons. In the field of prion diseases, however, insights into the molecular basis and the temporal evolution of prion neurotoxicity are increasing. Re... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=2738408 Thu, 27 Aug 2009 22:10:05 +0100 2738408 http://www.medworm.com/index.php?rid=2716469&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19689304%26dopt%3DAbstract Authors: Arias-Carrión O, Bradbury M PMID: 19689304 [PubMed - in process] (Source: CNS and Neurological Disorders Drug Targets) CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=2716469 Fri, 31 Jul 2009 23:00:00 +0100 2716469 http://www.medworm.com/index.php?rid=2716468&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19689305%26dopt%3DAbstract Authors: García-García F, Acosta-Peña E, Venebra-Muñoz A, Murillo-Rodríguez E Kuniomi Ishimori and Henri Piéron were the first researchers to introduce the concept and experimental evidence for a chemical factor that would presumably accumulate in the brain during waking and eventually induce sleep. This substance was named hypnotoxin. Currently, the variety of substances which have been shown to alter sleep includes peptides, cytokines, neurotransmitters and some substances of lipidic nature, many of which are well known for their involvement in other biological activities. In this chapter, we describe the sleep-inducing properties of the vasoactive intestinal peptide, prolactin, adenosine and anandamide. PMID: 19689305 [PubMed - in process] (Source: ... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=2716468 Fri, 31 Jul 2009 23:00:00 +0100 2716468 http://www.medworm.com/index.php?rid=2716467&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19689306%26dopt%3DAbstract Authors: Murillo-Rodríguez E, Arias-Carrión O, Sanguino-Rodríguez K, González-Arias M, Haro R Regulation of the sleep-waking cycle is complex, involving multiple neurological circuits and diverse endogenous molecules. Interplay among assorted neuroanatomical and neurochemical systems such as acetylcholine, dopamine, noradrenaline, serotonin, histamine, and hypocretin maintain the waking (W) state. The sleep-onset is governed by the interacting forces of the sleep drive, which steadily increases with duration of W, and circadian fluctuations. Sleep-promoting neurons located in the anterior hypothalamus release GABA and inhibit wake-promoting regions in the hypothalamus and brainstem and participate in the generation of slow wave sleep (SWS). During rapid eye movement... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=2716467 Fri, 31 Jul 2009 23:00:00 +0100 2716467 http://www.medworm.com/index.php?rid=2716466&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19689307%26dopt%3DAbstract Authors: Dang-Vu TT, Desseilles M, Schwartz S, Maquet P Neuroimaging techniques have refined the characterization of neural structures involved in the regulation of normal sleep-wake cycle in healthy humans. Yet brain imaging studies in patients with sleep disorders still remain scarce. In narcoleptic patients, structural and functional brain imaging studies have suggested the involvement of the hypothalamus in the pathophysiology of narcolepsy, plausibly consistent with an impairment of the hypocretin-orexin system. Some recent studies have further suggested that cataplexy, a key feature of the narcoleptic syndrome, might result from a dysfunction of the hypothalamus and its interactions with limbic structures. Other neuroimaging studies have focused on the assessment of neurotransmis... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=2716466 Fri, 31 Jul 2009 23:00:00 +0100 2716466 http://www.medworm.com/index.php?rid=2716465&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19689308%26dopt%3DAbstract Authors: Billiard M REM (rapid eye movement) sleep behavior disorder (RBD) is a well known parasomnia [1]. Its first description in humans dates back to 1985, and its first description in narcoleptic patients to 1992. Although the precise pathophysiology of RBD remains unclear, it is likely, in the case of RBD associated with narcolepsy, that the altered function of hypocretin pathways projecting from the lateral hypothalamus to the ventrolateral part of the periaqueductal grey matter and the lateral pontine tegmentum has a consistent role. The percentage of narcoleptic patients complaining of clinical RBD lies somewhere between 10 and 15% of the narcoleptic population. The age of onset is younger than in the other forms of chronic RBD. Clinical features are the same as in the other fo... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=2716465 Fri, 31 Jul 2009 23:00:00 +0100 2716465 http://www.medworm.com/index.php?rid=2716464&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19689309%26dopt%3DAbstract Authors: Kroeger D, de Lecea L A series of discoveries spanning the last decade have uncovered a new neurotransmitter - hypocretin - and its role in energy metabolism, arousal, and addiction. Also, notably, a lack of hypocretin function has been unequivocally associated with the sleep disorder narcolepsy. Here we review these findings and discuss how they will influence future treatments of narcolepsy and other arousal and hyperarousal disorders. We introduce the concept of the hypocretin peptides and receptors and discuss the neuroanatomy and neurophysiology of the hypocretin system. A gain of function through pharmacolological and optogenetic means is also addressed in the following text, as is the loss of function: specifically narcolepsy in dogs, mice and humans and the challenges ... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=2716464 Fri, 31 Jul 2009 23:00:00 +0100 2716464 http://www.medworm.com/index.php?rid=2716463&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19689310%26dopt%3DAbstract Authors: Mieda M, Sakurai T Recent studies have established that the orexin system is a critical regulator of sleep/wake states. Deficiency of orexin signaling results in the sleep disorder narcolepsy-cataplexy in humans, dogs, and rodents. These findings have brought about the possibility of novel therapies for sleep disorders including narcolepsy-cataplexy. Furthermore, accumulating evidence has indicated that the orexin system regulates sleep and wakefulness through interactions with neuronal systems that regulate emotion, reward, and energy homeostasis. This review presents and discusses the current understanding of the integrative physiology of the orexin system. PMID: 19689310 [PubMed - in process] (Source: CNS and Neurological Disorders Drug Targets) CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=2716463 Fri, 31 Jul 2009 23:00:00 +0100 2716463 http://www.medworm.com/index.php?rid=2716462&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19689311%26dopt%3DAbstract Authors: Chen L, Brown RE, McKenna JT, McCarley RW Narcolepsy is a debilitating sleep disorder with excessive daytime sleepiness and cataplexy as its two major symptoms. Although this disease was first described about one century ago, an animal model was not available until the 1970s. With the establishment of the Stanford canine narcolepsy colony, researchers were able to conduct multiple neurochemical studies to explore the pathophysiology of this disease. It was concluded that there was an imbalance between monoaminergic and cholinergic systems in canine narcolepsy. In 1999, two independent studies revealed that orexin neurotransmission deficiency was pivotal to the development of narcolepsy with cataplexy. This scientific leap fueled the generation of several genetically engineered... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=2716462 Fri, 31 Jul 2009 23:00:00 +0100 2716462 http://www.medworm.com/index.php?rid=2716461&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19689312%26dopt%3DAbstract This article reviews the current understanding of narcolepsy and discusses the opportunity to explore the potential use of transplants as a therapeutical tool in order to treat narcolepsy. PMID: 19689312 [PubMed - in process] (Source: CNS and Neurological Disorders Drug Targets) CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=2716461 Fri, 31 Jul 2009 23:00:00 +0100 2716461 http://www.medworm.com/index.php?rid=2611979&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19601814%26dopt%3DAbstract Authors: Anlar O Multiple Sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system, with highly variable clinical course that most typically exhibits a relapsing-remitting pattern. Neuroimaging, pathological findings and response to available therapies are also not uniform. It commonly affects young adults and is usually characterized in the early years by acute relapses followed by partial or complete remission; in later years progressive and irreversible disability develops. The clinical course of MS is defined as relapsing-remitting (RRMS), primary progressive (PPMS), progressive relapsing (PRMS) and secondary progressive (SPMS). The treatment of RRMS is based on the use of immunosuppressive and immune-modulating therapy. Immunosuppressive agents ... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=2611979 Sun, 31 May 2009 23:00:00 +0100 2611979 http://www.medworm.com/index.php?rid=2611978&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19601815%26dopt%3DAbstract Authors: Bermejo PE, Anciones B Neuropathic pain is a phenomenon characterized by a high population prevalence by possessing several etiologies. In contrast to nociceptive pain, painful signals in neuropathic pain are originated in the nervous system, present poor responses to conventional treatments and may worsen the quality of life. Antiepileptic drugs are increasingly used for different purposes including migraine, neuropathic pain, tremor or psychiatric disorders and they have started to be called neuromodulators. These drugs may act on very different targets such as sodium, potassium or calcium channels, purinergic, GABAergic, glutamatergic or vanilloid receptors and different cytokines including IL-6 or TNF, each if which may be important in managing some aspects of neuropathic ... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=2611978 Sun, 31 May 2009 23:00:00 +0100 2611978 http://www.medworm.com/index.php?rid=2611977&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19601816%26dopt%3DAbstract CONCLUSIONS: Ligand-based antiangiogenic therapy (in particular bevacizumab) is a compelling new targeted therapy for HGG and will continue to emerge as an important novel anti-glioma therapy. Further studies are required to define the population of patients with HGG in whom this therapy is of benefit, identify the optimal dose and schedule, better characterize the value of co-administered (cytotoxic and targeted) therapies and establish validated response measures. PMID: 19601816 [PubMed - in process] (Source: CNS and Neurological Disorders Drug Targets) CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=2611977 Sun, 31 May 2009 23:00:00 +0100 2611977 http://www.medworm.com/index.php?rid=2611976&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19601817%26dopt%3DAbstract Authors: Gabathuler R The central nervous system is a sanctuary protected by barriers that regulate brain homeostasis and control the transport of endogenous compounds into the brain. The blood-brain barrier, formed by endothelial cells of the brain capillaries, restricts access to brain cells allowing entry only to amino acids, glucose and hormones needed for normal brain cell function and metabolism. This very tight regulation of brain cell access is essential for the survival of neurons which do not have a significant capacity to regenerate, but also prevents therapeutic compounds, small and large, from reaching the brain. As a result, various strategies are being developed to enhance access of drugs to the brain parenchyma at therapeutically meaningful concentrations to effectively... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=2611976 Sun, 31 May 2009 23:00:00 +0100 2611976 http://www.medworm.com/index.php?rid=2611975&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19601818%26dopt%3DAbstract Authors: Halliday AJ, Cook MJ Polymer based therapies offer many potential advantages in the treatment of diseases of the nervous system, and would allow delivery of therapeutic agents directly to the relevant area of brain, circumventing obstacles presented by the blood brain barrier, avoiding the side-effects often associated with systemic medication administration, and permitting much smaller doses of medication. As improvements in diagnostic procedures, particularly imaging, now provide very accurate localization of therapeutic targets in many of these conditions, it is technically feasible to deliver such agents precisely to the relevant brain region. Combined with advances in polymer sciences, there is renewed interest in focal drug delivery systems, particularly around intellige... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=2611975 Sun, 31 May 2009 23:00:00 +0100 2611975 http://www.medworm.com/index.php?rid=2611974&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19601819%26dopt%3DAbstract Authors: Orsucci D, Calsolaro V, Mancuso M, Siciliano G Tetracyclines are a class of antibiotics which could play a therapeutic role in several neurological disorders. Minocycline, extensively studied in animal models, decreased the size of ischaemic and haemorrhagic infarct. In Parkinson's disease models minocycline protected the nigrostriatal pathway, and in Huntington's disease and motoneuron disease models delayed the progression of disease extending the lifespan. Finally, in human diseases such as stroke and multiple sclerosis tetracyclines seem to play some neuroprotective role. The main biological effects of tetracyclines are the inhibition of microglial activation, the attenuation of apoptosis, and the suppression of reactive oxygen species production. These mechanisms are invo... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=2611974 Sun, 31 May 2009 23:00:00 +0100 2611974 http://www.medworm.com/index.php?rid=2532097&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19355929%26dopt%3DAbstract Authors: Cribbs DH, Agadjanyan MG PMID: 19355929 [PubMed - in process] (Source: CNS and Neurological Disorders Drug Targets) CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=2532097 Tue, 31 Mar 2009 23:00:00 +0100 2532097 http://www.medworm.com/index.php?rid=2532096&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19355930%26dopt%3DAbstract Authors: Kokjohn TA, Roher AE Post mortem examinations of AN-1792-vaccinated humans revealed this therapy produced focal senile plaque disruption. Despite the dispersal of substantial plaque material, vaccination did not constitute even a partial eradication of brain amyloid as water soluble amyloid-beta (Abeta) 40/42 increased in the gray matter compared to sporadic Alzheimer's disease (AD) patients and total brain Abeta levels were not decreased. Significant aspects of AD pathology were unaffected by vaccination with both vascular amyloid and hyper-phosphorylated tau deposits appeared refractory to this therapy. In addition, vaccination resulted in the consequential and drastic expansion of the white matter (WM) amyloid pool to levels without precedent in sporadic AD patients. Althou... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=2532096 Tue, 31 Mar 2009 23:00:00 +0100 2532096 http://www.medworm.com/index.php?rid=2532095&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19355931%26dopt%3DAbstract Authors: Vasilevko V, Head E Alzheimer disease (AD) is the most common form of dementia in the elderly and the number of individuals developing the disease is rapidly rising. Interventions focused on reducing beta-amyloid (Abeta), a component of senile plaques within the AD brain offer a promising approach to prevent or slow disease progression. In this review, we describe the immune system and cognitive and neurobiological features of a natural model of human brain aging, the beagle. The immune system of dogs shares many features of the human immune system, including developmental and aging characteristics. Further, dogs naturally accumulate human sequence Abeta as they age, which coincides with declines in learning and memory. A longitudinal study (approximately 2 years) of the respo... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=2532095 Tue, 31 Mar 2009 23:00:00 +0100 2532095 http://www.medworm.com/index.php?rid=2532094&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19355932%26dopt%3DAbstract Authors: Town T In a seminal report in 1999, Schenk and colleagues demonstrated that vaccination of a mouse model of Alzheimer's disease (AD) with amyloid-beta(1-42) peptide (Abeta(1-42)) and adjuvant resulted in striking mitigation of AD-like pathology - giving rise to the field of AD immunotherapy. Later studies confirmed this result in other mouse models of AD and additionally showed cognitive improvement after Abeta vaccination. Based on these results, early developmental clinical trials ensued to immunize AD patients with Abeta(1-42) plus adjuvant (so-called "active" Abeta immunotherapy; trade name AN-1792; Elan Pharmaceuticals, Dublin, Ireland). However, the phase IIa trial was halted after 6 % of patients developed aseptic meningoencephalitis. Despite occurrence of this adverse ... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=2532094 Tue, 31 Mar 2009 23:00:00 +0100 2532094 http://www.medworm.com/index.php?rid=2532093&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19355933%26dopt%3DAbstract Authors: Ghochikyan A Amyloid-beta (Abeta) immunotherapy has received considerable attention as a promising approach for reducing the level of Abeta in the CNS of Alzheimer's disease patients. However, the first Phase II clinical trial, for the immune therapy AN1792, was halted when a subset of those immunized with Abeta(42) developed adverse events in the central nervous system. In addition, data from the trial indicated that there was a low percentage of responders and generally low to moderate titers in the patients that received the vaccine. Generated antibodies reduced beta-amyloid deposits in the parenchyma of patients' brains, but no reduction in soluble Abeta or significant improvements in cognitive function of patients were observed. These data and data from pre-clinical studi... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=2532093 Tue, 31 Mar 2009 23:00:00 +0100 2532093 http://www.medworm.com/index.php?rid=2532092&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19355934%26dopt%3DAbstract Authors: Tarawneh R, Holtzman DM Over the last 10 years, promising data has emerged from both animal and human studies that both active immunization with amyloid-beta (Abeta) as well as passive immunization with anti-Abeta antibodies offer promise as therapies for Alzheimer's disease (AD). Data from animal models suggests that antibodies to Abeta through several mechanisms can decrease Abeta deposition, decrease Abeta -associated damage such as dystrophic neurite formation, and improve behavioral performance. Data from human studies suggests that active immunization can result in plaque clearance and that passive immunotherapy might result in slowing of cognitive decline. Despite this, a recent analysis from a phase I trial that involved active immunization with Abeta42, while not powe... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=2532092 Tue, 31 Mar 2009 23:00:00 +0100 2532092 http://www.medworm.com/index.php?rid=2532091&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19355935%26dopt%3DAbstract Authors: Wisniewski T PMID: 19355935 [PubMed - in process] (Source: CNS and Neurological Disorders Drug Targets) CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=2532091 Tue, 31 Mar 2009 23:00:00 +0100 2532091 http://www.medworm.com/index.php?rid=2263671&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19275632%26dopt%3DAbstract Authors: Agadjanyan MG, Cribbs DH PMID: 19275632 [PubMed - in process] (Source: CNS and Neurological Disorders Drug Targets) CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=2263671 Sun, 01 Mar 2009 05:00:00 +0100 2263671 http://www.medworm.com/index.php?rid=2263668&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19275633%26dopt%3DAbstract Authors: Morgan D Immunotherapy has emerged as a leading new approach to the reduction of amyloid deposits in the brains of Alzheimer patients. At least 4 distinct actions of anti-Abeta antibodies have been proposed as contributing to the inhibition of amyloid deposition and its clearance. Critically, each of these proposed mechanisms may be acting simultaneously, and it is feasible that different antibodies may utilize each mechanism to a different extent. One of these proposed mechanisms involves the activation of microglia and the phagocytosis of Abeta peptide. In general this is assumed to proceed through the Fcgamma-receptor binding by antibody opsonized Abeta aggregates, however modifying the microglial phenotype into one with a greater propensity for phagocytosing Abeta is also ... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=2263668 Sun, 01 Mar 2009 05:00:00 +0100 2263668 http://www.medworm.com/index.php?rid=2263664&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19275634%26dopt%3DAbstract Authors: Deane R, Bell RD, Sagare A, Zlokovic BV The main receptors for amyloid-beta peptide (Abeta) transport across the blood-brain barrier (BBB) from brain to blood and blood to brain are low-density lipoprotein receptor related protein-1 (LRP1) and receptor for advanced glycation end products (RAGE), respectively. In normal human plasma a soluble form of LRP1 (sLRP1) is a major endogenous brain Abeta 'sinker' that sequesters some 70 to 90 % of plasma Abeta peptides. In Alzheimer's disease (AD), the levels of sLRP1 and its capacity to bind Abeta are reduced which increases free Abeta fraction in plasma. This in turn may increase brain Abeta burden through decreased Abeta efflux and/or increased Abeta influx across the BBB. In Abeta immunotherapy, anti-Abeta antibody sequestration of... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=2263664 Sun, 01 Mar 2009 05:00:00 +0100 2263664 http://www.medworm.com/index.php?rid=2263660&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19275635%26dopt%3DAbstract Authors: Golde TE, Das P, Levites Y There is substantial and compelling evidence that aggregation and accumulation of amyloid beta protein (Abeta) plays a pivotal role in the development of Alzheimer's disease (AD); thus, numerous strategies to prevent Abeta aggregation and accumulation or to facilitate removal of preexisting deposits of Abeta are being evaluated as ways to treat or prevent AD. Pre-clinical studies in mice demonstrate the therapeutic potential of altering Abeta deposition by inducing a humoral immune response to fibrillar Abeta42 (fAbeta42) or passively administering anti-Abeta antibodies (Abs), and both passive and active anti-Abeta immunotherapeutic approaches are now being tested in humans. Although a variety of mechanisms have been postulated regarding how Abeta im... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=2263660 Sun, 01 Mar 2009 05:00:00 +0100 2263660 http://www.medworm.com/index.php?rid=2263657&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19275636%26dopt%3DAbstract Authors: Wilcock DM, Colton CA Alzheimer's disease (AD) is a progressive, neurodegenerative disorder that results in severe cognitive decline. Amyloid plaques are a principal pathology found in AD and are composed of aggregated amyloid-beta (Abeta) peptides. According to the amyloid hypothesis, Abeta peptides initiate the other pathologies characteristic for AD including cognitive deficits. Immunotherapy against Abeta is a potential therapeutic for the treatment of humans with AD. While anti-Abeta immunotherapy has been shown to reduce amyloid burden in both mouse models and in humans, immunotherapy also exacerbates vascular pathologies. Cerebral amyloid angiopathy (CAA), that is, the accumulation of amyloid in the cerebrovasculature, is increased with immunotherapy in humans with AD a... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=2263657 Sun, 01 Mar 2009 05:00:00 +0100 2263657 http://www.medworm.com/index.php?rid=2263654&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19275637%26dopt%3DAbstract Authors: Lambert MP, Velasco PT, Viola KL, Klein WL Individuals with early Alzheimer's disease (AD) suffer from a selective and profound failure to form new memories. A novel molecular mechanism with implications for therapeutics and diagnostics is now emerging in which the specificity of AD for memory derives from disruption of plasticity at synapses targeted by toxic Abeta oligomers (also known as ADDLs). ADDLs accumulate in AD brain and constitute long-lived alternatives to the disease-defining Abeta fibrils deposited in amyloid plaques. The AD-like cellular pathologies induced by ADDLs suggest their impact could provide a unifying mechanism for AD pathogenesis, explaining why early stage disease is specific for memory and accounting for major facets of AD neuropathology. Discovery ... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=2263654 Sun, 01 Mar 2009 05:00:00 +0100 2263654 http://www.medworm.com/index.php?rid=2093358&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19128206%26dopt%3DAbstract Authors: Adams JD This review discusses new mechanisms for the induction of Alzheimer's disease, involving lipid toxicity and adipokines. Ceramide induces oxidative stress and the formation of amyloid beta. Visfatin induces oxidative stress, damages the blood brain barrier and increases the attraction of monocytes, neutrophils and other white blood cells. A new mechanism for visfatin/NAD (nicotinamide adenine dinucleotide)-induced oxidative stress is presented involving redox cycling catalyzed by xanthine dehydrogenase and NADH oxidase. These mechanisms are discussed in terms of the treatment of Alzheimer's disease. PMID: 19128206 [PubMed - in process] (Source: CNS and Neurological Disorders Drug Targets) CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=2093358 Mon, 01 Dec 2008 05:00:00 +0100 2093358 http://www.medworm.com/index.php?rid=2093357&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19128207%26dopt%3DAbstract Authors: Becker RE, Greig NH Alzheimer's disease (AD) clinical drug development and patient care depend on rating instruments, research designs and methods, and translations of clinical trial (CT) results into the clinic without support from standardized protocols able to control (i) random measurement error intrusions into observations, (ii) inaccuracy and bias introduced by clinical evaluators, (iii) conformity of research sites to conditions of research protocols, (iv) the ability of the CT to model for practitioners the most effective use of the drug with individual patients, and (v) other factors able to invalidate research and patient care data. This relaxed attitude with regard to AD methods may be changing now with Alzheimer's Disease Neuroimaging Initiative (ADNI) evidence tha... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=2093357 Mon, 01 Dec 2008 05:00:00 +0100 2093357 http://www.medworm.com/index.php?rid=2093356&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19128208%26dopt%3DAbstract Authors: Chen LW, Yung KK, Chan YS, Shum DK, Bolam JP Growing evidence has shown that the p75 neurotrophin receptor (p75NTR) may play important roles in controlling neuronal survival or cell apoptosis within the central nervous system in development, and in pathological or neural injury. Recent studies have further revealed that p75NTR acts as a "molecular signal switch" that determines cell death or survival by three processes. First, pro-nerve growth factor (proNGF) triggers cell apoptosis by its high affinity binding to p75NTR, while NGF induces neuronal survival with low-affinity binding. Second, p75NTR mediates cell death by combining with co-receptor sortilin, whereas it promotes neuronal survival through combination with proNGF. Third, release of the intracellular domain chopper... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=2093356 Mon, 01 Dec 2008 05:00:00 +0100 2093356 http://www.medworm.com/index.php?rid=2093355&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19128209%26dopt%3DAbstract In this study we aim to review the factors concurrent with an increase in central sensitisation, in view of the choice of preventive agents for primary headaches. Central sensitisation phenomena are increased in pain syndromes with psycho-pathological co-morbidities. For instance, sleep disorders are a frequent symptom in headache, prevailing in chronic forms and in patients with psychiatric comorbidity. Sleep deprivation is also a factor producing hyperalgesic changes. It is known that symptoms attributable to central sensitization are diffusely pronounced in fibromyalgic (FMS) patients, and that FMS co-morbidity is frequent in primary headaches and associated with higher frequency and poorer quality of life. We report our preliminary experience in a group of 20 chronic migraine patients,... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=2093355 Mon, 01 Dec 2008 05:00:00 +0100 2093355 http://www.medworm.com/index.php?rid=2093354&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19128210%26dopt%3DAbstract Authors: Yan J, Greer JM Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease of the central nervous system (CNS) that afflicts over 2 million people worldwide. On the basis of the temporal course of disease, MS can be subdivided into three clinical groups: relapsing remitting MS (RR-MS), secondary progressive MS and primary progressive MS. There is a high degree of clinical diversity within these subgroups. The pathogenesis of MS in most patients is likely to result from autoreactive, activated CD4(+) T cells moving from the periphery across the blood brain barrier into the CNS. Most therapeutic agents used in MS (e.g. immunosuppressive and immunomodulatory drugs and cell cycle interruption drugs) are only used for RR-MS. These treatments show some efficiency in lessen... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=2093354 Mon, 01 Dec 2008 05:00:00 +0100 2093354 http://www.medworm.com/index.php?rid=2093366&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19128198%26dopt%3DAbstract Authors: Rahman S PMID: 19128198 [PubMed - in process] (Source: CNS and Neurological Disorders Drug Targets) CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=2093366 Sat, 01 Nov 2008 04:00:00 +0100 2093366 http://www.medworm.com/index.php?rid=2093365&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19128199%26dopt%3DAbstract Authors: Zhu J, Reith ME A number of studies over the last two decades have demonstrated the critical importance of dopamine (DA) in the behavioral pharmacology and addictive properties of abused drugs. The DA transporter (DAT) is a major target for drugs of abuse in the category of psychostimulants, and for methylphenidate (MPH), a drug used for treating attention deficit hyperactivity disorder (ADHD), which can also be a psychostimulant drug of abuse. Other drugs of abuse such as nicotine, ethanol, heroin and morphine interact with the DAT in more indirect ways. Despite the different ways in which drugs of abuse can affect DAT function, one evolving theme in all cases is regulation of the DAT at the level of surface expression. DAT function is dynamically regulated by multiple intrac... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=2093365 Sat, 01 Nov 2008 04:00:00 +0100 2093365 http://www.medworm.com/index.php?rid=2093364&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19128200%26dopt%3DAbstract Authors: Heidbreder C The focal distribution of the dopamine (DA) D(3) receptor in brain regions implicated in emotional and cognitive functions has made this target a main focus of drug discovery efforts. This paper will review the most recent lines of research in support of the use of selective DA D(3) receptor antagonists for the pharmacotherapeutic management of drug addiction: (1) expression of the DA D(3) receptor in the rodent and human brain; (2) changes in expression of the DA D(3) receptor following exposure to drugs of abuse, and (3) efficacy of selective DA D(3) receptor antagonists in preclinical paradigms assessing the behavioral effects of drugs such as cocaine, nicotine, alcohol, methamphetamine, and heroin. This manuscript, however, will not review the effects of nonse... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=2093364 Sat, 01 Nov 2008 04:00:00 +0100 2093364 http://www.medworm.com/index.php?rid=2093363&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19128201%26dopt%3DAbstract Authors: Rahman S, López-Hernández GY, Corrigall WA, Papke RL Nicotine addiction and other forms of drug addiction continue to be significant public health problems in the United States and the rest of the world. Accumulated evidence indicates that brain nicotinic acetylcholine receptors (nAChRs) are a heterogenous family of ion channels expressed in the various parts of the brain. A growing body of preclinical studies suggests that brain nAChRs are critical targets for the development of pharmacotherapies for nicotine and other drug addictions. In this review, we will discuss the nAChR subtypes, their function in response to endogenous brain transmitters, and how their functions are regulated in the presence of nicotine. Furthermore, we will discuss the role of nAChRs in med... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=2093363 Sat, 01 Nov 2008 04:00:00 +0100 2093363 http://www.medworm.com/index.php?rid=2093362&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19128202%26dopt%3DAbstract This article will review data suggesting an important role of mu-opioid receptor (MOPr) and delta opioid receptor (DOPr) systems in mediating the rewarding effects of several classes of abused drugs and that aberrant activity of these opioid systems may not only contribute to the behavioral dysregulation that characterizes addiction but to individual differences in addiction vulnerability. PMID: 19128202 [PubMed - in process] (Source: CNS and Neurological Disorders Drug Targets) CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=2093362 Sat, 01 Nov 2008 04:00:00 +0100 2093362 http://www.medworm.com/index.php?rid=2093361&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19128203%26dopt%3DAbstract Authors: Engleman EA, Rodd ZA, Bell RL, Murphy JM Alcohol and drug abuse continue to be a major public health problem in the United States and other industrialized nations. Extensive preclinical research indicates the mesolimbic dopamine (DA) pathway and associated regions mediate the rewarding and reinforcing effects of drugs of abuse and natural rewards, such as food and sex. The serotonergic (5-HT) system, in concert with others neurotransmitter systems, plays a key role in modulating neuronal systems within the mesolimbic pathway. A substantial portion of this modulation is mediated by activity at the 5-HT3 receptor. The 5-HT3 receptor is unique among the 5-HT receptors in that it directly gates an ion channel inducing rapid depolarization that, in turn, causes the release of neuro... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=2093361 Sat, 01 Nov 2008 04:00:00 +0100 2093361 http://www.medworm.com/index.php?rid=2093360&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19128204%26dopt%3DAbstract Authors: Scherma M, Fadda P, Le Foll B, Forget B, Fratta W, Goldberg SR, Tanda G Tobacco addiction is one of the leading preventable causes of mortality in the world and nicotine appears to be the main critical psychoactive component in establishing and maintaining tobacco dependence. Several lines of evidence suggest that the rewarding effects of nicotine, which underlie its abuse potential, can be modulated by manipulating the endocannabinoid system. For example, pharmacological blockade or genetic deletion of cannabinoid CB(1) receptors reduces or eliminates many behavioral and neurochemical effects of nicotine that are related to its addictive potential. This review will focus on the recently published literature about the role of the endocannabinoid system in nicotine addiction an... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=2093360 Sat, 01 Nov 2008 04:00:00 +0100 2093360 http://www.medworm.com/index.php?rid=2093359&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19128205%26dopt%3DAbstract Authors: Uys JD, LaLumiere RT Considerable research into the neurobiology of cocaine addiction has shed light on the role of glutamate. Findings from models of relapse to cocaine-seeking indicate that the glutamatergic system is critically involved, as glutamate levels in the nucleus accumbens increase during reinstatement and glutamate receptor activation is necessary for reinstatement to drug-seeking. Thus, it would seem beneficial to block the increased glutamate release, but full antagonists of ionotropic glutamate receptors produce undesirable side effects. Therefore, modulation of glutamatergic transmission would be advantageous and provide novel pharmacotherapeutic avenues. Pharmacotherapies have been developed that have the potential to modulate excessive glutamatergic transmis... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=2093359 Sat, 01 Nov 2008 04:00:00 +0100 2093359 http://www.medworm.com/index.php?rid=1952980&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18991661%26dopt%3DAbstract Authors: Abdel-Salam OM Parkinson's disease (PD) is the second most common neurodegenerative disorder, after Alzheimer's disease. In PD, motor symptoms result from the degeneration and loss of pigmented dopaminergic neurons of the substantia nigra pars compacta of the basal ganglia. Other neuronal fields and neurotransmitter systems are also involved, including non-adrenergic, serotonergic and cholinergic neurons. Since the early 1960s the treatment of PD has been based on the pharmacologic replacement of dopamine accomplished with the precursor of dopamine, 3, 4-dihydroxy-L-phenylalanine (L-dopa). The addition of carbidopa, an inhibitor of the decarboxylase represented a tremendous improvement in therapy and is still a mainstay of the treatment of PD. Dopamine agonists may also be use... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=1952980 Wed, 01 Oct 2008 04:00:00 +0100 1952980 http://www.medworm.com/index.php?rid=1952979&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18991662%26dopt%3DAbstract Authors: Ali A, Ahmad FJ, Dua Y, Pillai KK, Vohora D Advances in the understanding of mechanisms underlying the pathophysiology of epilepsy have led to the identification of sodium hydrogen exchanger (NHE) as one of the possible targets for future antiepileptic drugs (AEDs). There are indicators from several experimental studies that NHE inhibitors could be of significant value as potential anticonvulsants. Various in-vitro reports (brain slices) have suggested anticonvulsant potential of these agents. Recently we provided the in-vivo data on anticonvulsant efficacy of amiloride (an NHE inhibitor) in different animal models of seizure and epilepsy. In addition to blocking NHE, these agents are known to affect other traditional targets like voltage-gated Na(+) channels, Ca(2+) channels,... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=1952979 Wed, 01 Oct 2008 04:00:00 +0100 1952979 http://www.medworm.com/index.php?rid=1952978&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18991663%26dopt%3DAbstract Authors: Carozzi V, Marmiroli P, Cavaletti G The role of Glutamate (Glu), one of the major excitatory neurotransmitters in the central nervous system, has been thoroughly investigated in animal models and in humans in several physiologic events, such as brain development and synaptic plasticity, but also in acute and chronic neurologic diseases and psychiatric disorders. Recently, it has been demonstrated that Glu is important for sensory input transduction, particularly along the nociceptive pathway. Glu involvement in peripheral neuropathies has also been suggested on the basis of experimental studies in animals, thus widening the spectrum of possible sites of action of this neurotransmitter from the central to the peripheral nervous system. This rather unexpected observation may hav... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=1952978 Wed, 01 Oct 2008 04:00:00 +0100 1952978 http://www.medworm.com/index.php?rid=1952977&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18991664%26dopt%3DAbstract Authors: Carroll JE, Borlongan CV Adult stem cell therapy has been proposed for brain injury in young children. While there have been no clinical trials in the US, the therapy is widely advertised and anecdotally reported in multiple internet sources, leading families to seek the treatment in uncontrolled circumstances. The purpose of this review is to present a discussion of the various types of stem cell preparations, with emphasis on adult stem cells, the scientific basis of their development, and the available experimental evidence for their utility in childhood brain injury. We will also provide background information on the biologic events occurring in injured immature brain, as they relate to the transplantation of stem cells. We will then review our own data from neonatal roden... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=1952977 Wed, 01 Oct 2008 04:00:00 +0100 1952977 http://www.medworm.com/index.php?rid=1952976&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18991665%26dopt%3DAbstract Authors: De Vivo G, Gentile V Transglutaminases are a large family of related and ubiquitous enzymes which catalyze the cross-linking of a glutaminyl residue of a protein/peptide substrate to a lysyl residue of a protein/peptide co-substrate. These enzymes are also capable of catalyzing other reactions important for the cell viability. The distribution and the physiological roles of the human transglutaminases have been widely studied in numerous cell types and tissues and their roles in several diseases have begun to be identified. Recently, "tissue" transglutaminase (TG2) has been shown to be involved in the molecular mechanisms responsible for a very widespread human pathology, Celiac Disease (CD). Transglutaminase activity has also been hypothesized to be directly involved in the p... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=1952976 Wed, 01 Oct 2008 04:00:00 +0100 1952976 http://www.medworm.com/index.php?rid=1952975&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18991666%26dopt%3DAbstract Authors: Miyaoka T Minocycline, an antibiotic of the tetracycline family, has been shown to display neurorestorative or neuroprotective properties in various models of neurodegenerative diseases. In particular, it has been shown to delay motor alterations, inflammation and apoptosis in models of Huntington's disease, amyotrophic lateral sclerosis and Parkinson's disease. Despite controversies about its efficacy, the relative safety and tolerability of minocycline have led to various clinical trials. Recently, we reported the antipsychotic effects of minocycline in patients with schizophrenia. In a pilot investigation, we administered minocycline as an open-label adjunct to antipsychotic medication to patients with schizophrenia. The results of this trial suggested that minocycline migh... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=1952975 Wed, 01 Oct 2008 04:00:00 +0100 1952975 http://www.medworm.com/index.php?rid=1952974&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18991667%26dopt%3DAbstract Authors: Marini AM, Popolo M, Pan H, Blondeau N, Lipsky RH A variety of sublethal or stressful stimuli induce a phenomenon in the brain known as tolerance, an adaptive response that protects the brain against the same stress, or against a different stress (cross-tolerance). Understanding the molecular mechanisms of brain preconditioning holds promise in developing innovative therapies to prevent and treat neurodegenerative disorders, particularly ischemic stroke. Many of the detailed steps involved in tolerance and cross-tolerance are unknown. It is also likely that different stressors differentially regulate sets of genes, transcription factors, and signal transduction pathways that depend upon the molecules that are released in response to the stressor, activation of particular recep... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=1952974 Wed, 01 Oct 2008 04:00:00 +0100 1952974 http://www.medworm.com/index.php?rid=1680165&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18673206%26dopt%3DAbstract Authors: Ray SK PMID: 18673206 [PubMed - in process] (Source: CNS and Neurological Disorders Drug Targets) CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=1680165 Tue, 01 Jul 2008 04:00:00 +0100 1680165 http://www.medworm.com/index.php?rid=1680164&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18673207%26dopt%3DAbstract Authors: Liu XB, Wang JA, Yu SP, Keogh CL, Wei L Erythropoietin (EPO) was first identified as a hematopoietic cytokine that stimulates proliferation and differentiation of erythroid progenitor cells and was approved by the Food and Drug Administration as a treatment for chronic renal disease patients with anemia. In neural tissues, EPO is working via EPO receptors and induces non-hematopoietic effects. Recent studies have demonstrated that EPO exerts therapeutic potentials on neurological disorders such as ischemic stroke, intracerebral hemorrhage, subarachnoid hemorrhage, traumatic brain injury, and Parkinson's disease. EPO treatment has been shown to reduce the ischemic infarct and hemorrhage volume, decrease neuronal death including apoptosis, and improve survival rates in animal mo... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=1680164 Tue, 01 Jul 2008 04:00:00 +0100 1680164 http://www.medworm.com/index.php?rid=1680163&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18673208%26dopt%3DAbstract Authors: Wang X, Rosell A, Lo EH To date, tPA-based thrombolytic therapy is the only FDA-approved treatment for achieving vascular reperfusion and clinical benefit, but this agent is given to only about 2-5% of stroke patients in the United States of America. This may be related, in part, to the elevated risks of symptomatic intracranial hemorrhage, and the consequently reduced therapeutic time window. Recent efforts have aimed at identifying new combination strategies that might increase thrombolytic efficacy of tPA to benefit reperfusion, while reducing its associated neurotoxicity and hemorrhagic complications. Emerging experimental studies demonstrate that the breakdown of neurovascular matrix initiates blood-brain barrier disruption with edema and/or hemorrhage. Perturbation of ex... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=1680163 Tue, 01 Jul 2008 04:00:00 +0100 1680163 http://www.medworm.com/index.php?rid=1680162&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18673209%26dopt%3DAbstract Authors: Adibhatla RM, Hatcher JF Today there exists only one FDA-approved treatment for ischemic stroke; i.e., the serine protease tissue-type plasminogen activator (tPA). In the aftermath of the failed stroke clinical trials with the nitrone spin trap/radical scavenger, NXY-059, a number of articles raised the question: are we doing the right thing? Is the animal research truly translational in identifying new agents for stroke treatment? This review summarizes the current state of affairs with plasminogen activators in thrombolytic therapy. In addition to therapeutic value, potential side effects of tPA also exist that aggravate stroke injury and offset the benefits provided by reperfusion of the occluded artery. Thus, combinational options (ultrasound alone or with microspheres/nan... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=1680162 Tue, 01 Jul 2008 04:00:00 +0100 1680162 http://www.medworm.com/index.php?rid=1680161&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18673210%26dopt%3DAbstract Authors: Titsworth WL, Liu NK, Xu XM Secretory phospholipases A(2) (sPLA(2)s) are a subfamily of lipolytic enzymes which hydrolyze the acyl bond at the sn-2 position of glycerophospholipids to produce free fatty acids and lysophospholipids. These products are precursors of bioactive eicosanoids and platelet-activating factor (PAF). The hydrolysis of membrane phospholipids by PLA(2) is a rate-limiting step for generation of eicosanoids and PAF. To date, more than 10 isozymes of sPLA(2) have been found in the mammalian central nervous system (CNS). Under physiological conditions, sPLA(2)s are involved in diverse cellular responses, including host defense, phospholipid digestion and metabolism. However, under pathological situations, increased sPLA(2) activity and excessive production of ... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=1680161 Tue, 01 Jul 2008 04:00:00 +0100 1680161 http://www.medworm.com/index.php?rid=1680160&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18673211%26dopt%3DAbstract This article also focused on the role of cathepsin inhibitors as disease-modifying treatment strategies that could halt, or even prevent, this devastating neurological disorder. PMID: 18673211 [PubMed - in process] (Source: CNS and Neurological Disorders Drug Targets) CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=1680160 Tue, 01 Jul 2008 04:00:00 +0100 1680160 http://www.medworm.com/index.php?rid=1680159&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18673212%26dopt%3DAbstract Authors: Venugopal C, Demos CM, Rao KS, Pappolla MA, Sambamurti K The most popular current hypothesis is that Alzheimer's disease (AD) is caused by aggregates of the amyloid peptide (Abeta), which is generated by cleavage of the Abeta protein precursor (APP) by beta-secretase (BACE-1) followed by gamma-secretase. BACE-1 cleavage is limiting for the production of Abeta, making it a particularly good drug target for the generation of inhibitors that lower Abeta. A landmark discovery in AD was the identification of BACE-1 (a.k.a. Memapsin-2) as a novel class of type I transmembrane aspartic protease. Although BACE-2, a homologue of BACE-1, was quickly identified, follow up studies using knockout mice demonstrated that BACE-1 was necessary and sufficient for most neuronal Abeta generation.... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=1680159 Tue, 01 Jul 2008 04:00:00 +0100 1680159 http://www.medworm.com/index.php?rid=1680158&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18673213%26dopt%3DAbstract We present a general review of calpain-1 and an account of vast differences in processing of calpain-1 in the trabecular meshwork (trade mark) and the optic nerve. Calpain-1 accumulates in the glaucomatous trade mark tissues in vivo. However, calpain-1 activity is substantially lower in the glaucomatous trade mark compared to controls, apparently owing to partial degradation, and modification by lipid oxidation products such as iso [4]levuglandin E2 (iso [4]LGE(2)). Treatment of calpain-1 with iso [4]LGE(2) in vitro results in covalent modification, inactivation, and resistance to protease digestion. Iso [4]LGE(2)-modified calpain-1 appeared to undergo ubiquitination in the trade mark by cellular degradation machinery mediated by ubch1-2, ubch5,6 and E6-AP, E2 and E3 enzymes respectively. ... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=1680158 Tue, 01 Jul 2008 04:00:00 +0100 1680158 http://www.medworm.com/index.php?rid=1680157&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18673214%26dopt%3DAbstract Authors: Samantaray S, Ray SK, Banik NL Pathophysiology of idiopathic Parkinson's disease (PD) is associated with degeneration of dopaminergic neurons and inflammatory responses in the mid-brain substantia nigra (SN). However, central dopaminergic replenishment therapeutic strategy with L-3,4-dihydroxyphenylalanine (L-DOPA), the precursor for dopamine synthesis, does not fully rescue these cells in SN or improve motor function. Besides, prolonged use of L-DOPA worsens the clinical symptoms in PD patients. Thus, there is a possibility that other areas of central nervous system may also be affected in this disease. Spinal cord, the final coordinator of movement in the central nervous system, may be one such site that is critically affected during pathogenesis of this complex movement dis... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=1680157 Tue, 01 Jul 2008 04:00:00 +0100 1680157 http://www.medworm.com/index.php?rid=1680156&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18673215%26dopt%3DAbstract Authors: Das A, Guyton MK, Butler JT, Ray SK, Banik NL Experimental autoimmune encephalomyelitis (EAE), a widely recognized animal model of multiple sclerosis (MS), is highly useful for studying inflammation, demyelination, and neurodegeneration in the central nervous system (CNS). EAE exhibits many similarities with MS, which is a chronic inflammatory disease affecting CNS white matter in humans. Various studies have indicated that EAE is a particularly useful animal model for understanding both the mechanisms of immune-mediated CNS pathology and also the progressive clinical course of MS. Demyelination and axonal dysfunction have previously been shown in MS and EAE but current evidences indicate that axonal damage and neuron death also occur, demonstrating that these diseases harbor ... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=1680156 Tue, 01 Jul 2008 04:00:00 +0100 1680156 http://www.medworm.com/index.php?rid=1554952&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18537647%26dopt%3DAbstract Authors: Henschel O, Gipson KE, Bordey A GABA, acting via GABA(A) receptors, is well-accepted as the main inhibitory neurotransmitter of the mature brain, where it dampens neuronal excitability. The receptor's properties have been studied extensively, yielding important information about its structure, pharmacology, and regulation that are summarized in this review. Several GABAergic drugs have been commonly used as anesthetics, sedatives, and anticonvulsants for decades. However, findings that GABA has critical functions in brain development, in particular during the late embryonic and neonatal period, raise worthwhile questions regarding the side effects of GABAergic drugs that may lead to long-term cognitive deficits. Here, we will review some of these drugs in parallel with the con... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=1554952 Tue, 01 Apr 2008 04:00:00 +0100 1554952 http://www.medworm.com/index.php?rid=1510111&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18537640%26dopt%3DAbstract Authors: Krupp JJ PMID: 18537640 [PubMed - in process] (Source: CNS and Neurological Disorders Drug Targets) CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=1510111 Tue, 01 Apr 2008 04:00:00 +0100 1510111 http://www.medworm.com/index.php?rid=1510110&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18537641%26dopt%3DAbstract Authors: Dabrowski MA, Dekermendjian K, Lund PE, Krupp JJ, Sinclair J, Larsson O Ion channels are at present the third biggest target class in drug discovery. Primary research is continually uncovering potential new ion channel targets in indications such as cancer, diabetes and respiratory diseases, as well as the more established fields of pain, cardiovascular disease, and neurological disorders. Despite the physiological significance and therapeutic relevance in a wide variety of biological systems, ion channels still remain under exploited as drug targets. This is to a large extent resulting from the historical lack of screening technologies to provide the throughput and quality of data required to support medicinal chemistry. Although technical challenges still lie ahead, this his... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=1510110 Tue, 01 Apr 2008 04:00:00 +0100 1510110 http://www.medworm.com/index.php?rid=1510109&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18537642%26dopt%3DAbstract Ionotropic glutamate receptors & CNS disorders. CNS Neurol Disord Drug Targets. 2008 Apr;7(2):129-43 Authors: Bowie D Disorders of the central nervous system (CNS) are complex disease states that represent a major challenge for modern medicine. Although aetilogy is often unknown, it is established that multiple factors such as defects in genetics and/or epigenetics, the environment as well as imbalance in neurotransmitter receptor systems are all at play in determining an individual's susceptibility to disease. Gene therapy is currently not available and therefore, most conditions are treated with pharmacological agents that modify neurotransmitter receptor signaling. Here, I provide a review of ionotropic glutamate receptors (iGluRs) and the roles they fulfill in numerous ... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=1510109 Tue, 01 Apr 2008 04:00:00 +0100 1510109 http://www.medworm.com/index.php?rid=1510108&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18537643%26dopt%3DAbstract Authors: Chahine M, Chatelier A, Babich O, Krupp JJ Voltage-gated sodium channels play an essential biophysical role in many excitable cells such as neurons. They transmit electrical signals through action potential (AP) generation and propagation in the peripheral (PNS) and central nervous systems (CNS). Each sodium channel is formed by one alpha-subunit and one or more beta-subunits. There is growing evidence indicating that mutations, changes in expression, or inappropriate modulation of these channels can lead to electrical instability of the cell membrane and inappropriate spontaneous activity observed during pathological states. This review describes the biochemical, biophysical and pharmacological properties of neuronal voltage-gated sodium channels (VGSC) and their implication ... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=1510108 Tue, 01 Apr 2008 04:00:00 +0100 1510108 http://www.medworm.com/index.php?rid=1510107&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18537644%26dopt%3DAbstract Authors: Cuypers E, Dabrowski M, Horoszok L, Terp GE, Tytgat J Over the last couple of years, transient receptor potential vanilloid 1(TRPV1) channels have been a hot topic in ion channel research. Since this research field is still rather new, there is not much known about the working mechanism of TRPV1 and its ligands. Nevertheless, the important physiological role and therapeutic potential are promising. Therefore, extensive research is going on and a lot of natural as well as synthetic compounds are already described. In this review, we briefly give an overview of capsaicin's history and the current knowledge of its working mechanism and physiological role. We discuss the best known plant molecules acting on TRPV1 and highlight the latest discovery in TRPV1 research: animal venoms ... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=1510107 Tue, 01 Apr 2008 04:00:00 +0100 1510107 http://www.medworm.com/index.php?rid=1510106&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18537645%26dopt%3DAbstract Authors: Schulte U Ion channels are integral membrane proteins that enable the passive flow of inorganic ions by forming hydrated pores across biological membranes. Their pore-forming alpha subunits determine ion permeation and provide the machinery for gating. In addition, channel class specific accessory proteins termed beta, gamma and delta subunits have been found that modulate or even determine key properties like channel gating (e.g. activation, inactivation properties), surface expression, targeting and stability. Moreover, some of these subunits constitute binding sites for toxins as well as for therapeutic drugs. With the development of more powerful proteomic and molecular biology-based methods, a vastly increasing number of proteins interacting with ion channels has recently... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=1510106 Tue, 01 Apr 2008 04:00:00 +0100 1510106 http://www.medworm.com/index.php?rid=1510105&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18537646%26dopt%3DAbstract Authors: Abdipranoto A, Wu S, Stayte S, Vissel B Neurodegenerative diseases are characterised by a net loss of neurons from specific regions of the central nervous system (CNS). Until recently, research has focused on identifying mechanisms that lead to neurodegeneration, while therapeutic approaches have been primarily targeted to prevent neuronal loss. This has had limited success and marketed pharmaceuticals do not have dramatic benefits. Here we suggest that the future success of therapeutic strategies will depend on consideration and understanding of the role of neurogenesis in the adult CNS. We summarize evidence suggesting that neurogenesis is impaired in neurodegenerative diseases such as Parkinson's, Alzheimer's and Amyotrophic Lateral Sclerosis, while it is enhanced in stroke... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=1510105 Tue, 01 Apr 2008 04:00:00 +0100 1510105 http://www.medworm.com/index.php?rid=1510104&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18537647%26dopt%3DAbstract Authors: Henschel O, Gipson KE, Bordey A GABA, acting via GABA(A) receptors, is well-accepted as the main inhibitory neurotransmitter of the mature brain, where it dampens neuronal excitability. The receptor's properties have been studied extensively, yielding important information about its structure, pharmacology, and regulation that are summarized in this review. Several GABAergic drugs have been commonly used as anesthetics, sedatives, and anticonvulsants for decades. However, findings that GABA has critical functions in brain development, in particular during the late embryonic and neonatal period, raise worthwhile questions regarding the side effects of GABAergic drugs that may lead to long-term cognitive deficits. Here, we will review some of these drugs in parallel with the con... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=1510104 Tue, 01 Apr 2008 04:00:00 +0100 1510104 http://www.medworm.com/index.php?rid=1483610&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18289025%26dopt%3DAbstract Authors: Di Matteo V, Esposito E, Di Giovanni G PMID: 18289025 [PubMed - in process] (Source: CNS and Neurological Disorders Drug Targets) CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=1483610 Fri, 01 Feb 2008 05:00:00 +0100 1483610 http://www.medworm.com/index.php?rid=1483609&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18289026%26dopt%3DAbstract Authors: Moreira PI, Santos MS, Oliveira CR, Shenk JC, Nunomura A, Smith MA, Zhu X, Perry G Oxidative stress occurs early in the progression of Alzheimer disease, significantly before the development of the pathologic hallmarks, neurofibrillary tangles and senile plaques. All classes of macromolecules (sugar, lipids, proteins, and nucleic acids) are affected by oxidative stress leading, inevitably, to neuronal dysfunction. Extensive data from the literature support the notion that mitochondrial and metal abnormalities are key sources of oxidative stress in Alzheimer disease. Furthermore, it has been suggested that in the initial stages of the development of Alzheimer disease, amyloid-beta deposition and hyperphosphorylated tau function as compensatory responses to ensure that neuronal ... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=1483609 Fri, 01 Feb 2008 05:00:00 +0100 1483609 http://www.medworm.com/index.php?rid=1483608&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18289027%26dopt%3DAbstract Authors: Tripathi VB, Al-Chalabi A Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease of motor neurons resulting in progressive paralysis and respiratory failure. About 1 in every 400 people dies of ALS, usually within 3 to 5 years of symptom onset. The lack of effective therapy means that although the incidence is comparable to that of multiple sclerosis, the prevalence is low. The causes of ALS are largely unknown, but the only disease-modifying therapy, riluzole, was designed based on one hypothesis of disease causation, the excitotoxic hypothesis. In this paper we will review current ideas about the causes of ALS and the therapeutic opportunities they suggest. PMID: 18289027 [PubMed - in process] (Source: CNS and Neurological Disorders Drug Targets) CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=1483608 Fri, 01 Feb 2008 05:00:00 +0100 1483608 http://www.medworm.com/index.php?rid=1483607&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18289028%26dopt%3DAbstract Authors: Qureshi GA, Qureshi AA, Devrajani BR, Chippa MA, Syed SA This review deals with the results showing the relation between vitamin B(12) deficiency and neurotoxicity of homocysteine and nitrite (a metabolite of nitric oxide) in Parkinson's patients treated with levodopa (L-Dopa). We have already reported a linear relationship between the CSF levels of nitrite with glutamic acid and homocysteine suggesting that the production of nitrite is interrelated with the neurotoxic level of homocysteine. The levels of nitrite and homocysteine resulting in the deficiency of vitamin B(12) are some of the factors promoting degeneration in Parkinson's disease. This review emphasizes the importance of these parameters in designing suitable drug therapy for Parkinson disease. Additionally, there... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=1483607 Fri, 01 Feb 2008 05:00:00 +0100 1483607 http://www.medworm.com/index.php?rid=1483606&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18289029%26dopt%3DAbstract Authors: Di Giovanni G Parkinson's disease (PD) is the second leading age-related degenerative brain disease in the world affecting millions of people. This neurological disorder disrupts the quality of life of patients and their families, exerts an enormous emotional and physical strain on caregivers, and has a large cost for society. Moreover, the increasing numbers of elderly people in the population will result in a sharp increase in the prevalence of PD. The understanding of its pathophysiology and treatment has advanced at a very impressive rate during past decades. Nevertheless, PD is still fatal and there is at present no cure for it. Furthermore, there are no proven therapies for prevention of PD and although evidence exists of risk and protective factors, this is not strong e... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=1483606 Fri, 01 Feb 2008 05:00:00 +0100 1483606 http://www.medworm.com/index.php?rid=1483605&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18289030%26dopt%3DAbstract Authors: Skaper SD PMID: 18289030 [PubMed - in process] (Source: CNS and Neurological Disorders Drug Targets) CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=1483605 Fri, 01 Feb 2008 05:00:00 +0100 1483605 http://www.medworm.com/index.php?rid=1483604&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18289031%26dopt%3DAbstract This article will provide an overview of neurotrophin biology, their receptors, and signalling pathways, followed by a description of functional mimetics of neurotrophins acting at Trk receptors. Moreover, exciting recent data describing G-protein-coupled receptor transactivation of Trk receptors and their downstream signalling pathways raise the possibility of using small molecules to elicit neuroprotective effects. PMID: 18289031 [PubMed - in process] (Source: CNS and Neurological Disorders Drug Targets) CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=1483604 Fri, 01 Feb 2008 05:00:00 +0100 1483604 http://www.medworm.com/index.php?rid=1483603&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18289032%26dopt%3DAbstract Authors: PMID: 18289032 [PubMed - in process] (Source: CNS and Neurological Disorders Drug Targets) CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=1483603 Fri, 01 Feb 2008 05:00:00 +0100 1483603 http://www.medworm.com/index.php?rid=1483602&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18289033%26dopt%3DAbstract Authors: Longo FM, Massa SM Ligand-independent and/or proNGF-induced p75(NTR) signaling has emerged as a potential major contributor to a number of pathological states, including axotomy-induced death, motor neuron degeneration, neuronal degeneration in Alzheimer's disease and oligodendrocyte death following spinal cord injury. A long standing goal in the neurotrophin field has been the development of non-peptide, small molecules capable of functioning as specific ligands at neurotrophin receptors such as p75(NTR) to promote desired biological outcomes. Synthetic peptides modeled on neurotrophin protein domains have been found to bind to and activate various neurotrophin receptors, raising the possibility that active, non-peptide, small molecule ligands might also be identified; howeve... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=1483602 Fri, 01 Feb 2008 05:00:00 +0100 1483602 http://www.medworm.com/index.php?rid=1483601&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18289034%26dopt%3DAbstract Authors: Mocchetti I, Brown M Neurotrophic factors, and in particular the neurotrophins, restore the function of damaged neurons and prevent apoptosis in adults. The potential therapeutic property of the neurotrophins is however, complicated by the peptidergic structure of these trophic factors, which impairs their penetration into the brain parenchyma, and therefore makes their pharmaco-therapeutic properties difficult to evaluate. In this article we will focus on the neurotrophin Brain-derived neurotrophic factor (BDNF) and its receptors to address various therapeutic strategies that may overcome this problem. We will call this strategy "small molecule approach" because it relies on increasing the function of endogenous neurotrophins by pharmacological compounds that induce synthesis... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=1483601 Fri, 01 Feb 2008 05:00:00 +0100 1483601 http://www.medworm.com/index.php?rid=1483600&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18289035%26dopt%3DAbstract Authors: Philpott KL, Facci L The signaling pathways which contribute to neuronal death during development, aging and disease have been extensively studied. While initial efforts focused on developmental death, increasing evidence suggests that mitogen-activated protein kinase pathways play a role in human pathology. In particular, the c-Jun N-terminal kinases (JNKs), mitogen-activated protein kinases activated by extracellular stimuli including stress, are a major focus. Knock-out mouse studies have demonstrated that removing particular JNK genes can reduce the severity in various disease scenarios, including those which are used to model Parkinson's disease and cerebral ischemia. In addition, activation of JNKs can be seen in human disease tissue. In this review we bring together the... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=1483600 Fri, 01 Feb 2008 05:00:00 +0100 1483600 http://www.medworm.com/index.php?rid=1483599&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18289036%26dopt%3DAbstract Authors: Khanna A, Shin S, Rao MS Embryonic stem cells (ESC) are a source of renewable cells, which possess a phenomenal potential to differentiate into a myriad of cell types. Thus, ESCs offer a potentially unlimited supply of cells, which can be deployed in developing cell-based therapies. The in vitro differentiation capacity of ESC into derivatives of the neuronal lineage has been demonstrated and the functionality of the ESC derived neuroprogenitors, upon transplantation into in vivo models has been substantiated. In this review, we discuss various approaches to directing ESC towards neural lineages and protocols for sorting and selection of differentiated progenies. We examine in particular in vitro differentiation of ESC to mid-brain dopaminergic (DA) neurons and glial cells and... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=1483599 Fri, 01 Feb 2008 05:00:00 +0100 1483599 http://www.medworm.com/index.php?rid=1483598&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18289037%26dopt%3DAbstract Authors: Molina-Holgado F, Doherty P, Williams G Neurotrophic factors comprise a broad family of secreted proteins that have growth promoting, survival promoting and differentiation inducing activities. Disruption of neurotrophic factor signalling is a characteristic of many central and peripheral nervous system disorders, such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis, stroke, and peripheral neuropathy and pain. It follows that treating patients with neurotrophic factors might be beneficial in a range of neurological diseases. However, the promising results seen in animal models of disease have not translated well into clinical trials due to the poor pharmacokinetics associated with the intact proteins, in particular, their short in... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=1483598 Fri, 01 Feb 2008 05:00:00 +0100 1483598 http://www.medworm.com/index.php?rid=1483616&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18220776%26dopt%3DAbstract Authors: Di Matteo V, Esposito E, Di Giovanni G PMID: 18220776 [PubMed - indexed for MEDLINE] (Source: CNS and Neurological Disorders Drug Targets) CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=1483616 Sat, 01 Dec 2007 05:00:00 +0100 1483616 http://www.medworm.com/index.php?rid=1483615&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18220777%26dopt%3DAbstract Authors: de Lago E, Fernández-Ruiz J Neuroprotective properties of cannabinoids have been extensively studied in the last years in different neurodegenerative pathologies. This potential is based on the antioxidant, anti-inflammatory and anti-excitotoxic properties exhibited by these compounds that allow them to afford neuroprotection in different neurodegenerative disorders like Parkinson's disease (PD), Huntington's disease (HD), multiple sclerosis (MS) and others. PD and HD are chronic pathologies that are caused by the degeneration of specific structures within the basal ganglia. In both disorders, the key mechanisms involved in the neuroprotection provided by cannabinoids include cannabinoid receptor-independent effects aimed at reducing the oxidative injury, and also cannabi... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=1483615 Sat, 01 Dec 2007 05:00:00 +0100 1483615 http://www.medworm.com/index.php?rid=1483614&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18220778%26dopt%3DAbstract Authors: Carnevale D, De Simone R, Minghetti L Reciprocal interactions between glia and neurons are essential for many critical functions in brain health and disease. Microglial cells, the brain resident macrophages, and astrocytes, the most prevalent type of cell in brain, are actively involved in the control of neuronal activities both in developing and adult organisms. At the same time, neurons influence glial functions, through direct cell-to-cell interactions as well as the release of soluble mediators. Among signals from neurons that may have an active role in controlling glial activation are two major neurotransmitters: acetylcholine and noradrenaline. Several studies indicate that microglia and astrocytes express adrenergic receptors, whose activation influences the release of ... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=1483614 Sat, 01 Dec 2007 05:00:00 +0100 1483614 http://www.medworm.com/index.php?rid=1483613&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18220779%26dopt%3DAbstract Authors: Pérez-De La Cruz V, Königsberg M, Santamaría A Kynurenine pathway is gaining more and more attention every day in biomedical research since this catabolic route for tryptophan decomposition is not only implicated in different neurological disorders, but also possesses neuroactive metabolites with different biological properties, such as pro-oxidant and antioxidant regulators. Thus, the intensive research on this metabolic pathway is helping us to understand those mechanisms underlying neurodegenerative events during the occurrence of pathological process in the central nervous system (CNS), thereby allowing the design of potential therapies for those disorders involving excitotoxic, oxidative and inflammatory components. Here we intend to provide a brief overvie... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=1483613 Sat, 01 Dec 2007 05:00:00 +0100 1483613 http://www.medworm.com/index.php?rid=1483612&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18220780%26dopt%3DAbstract Authors: Nunomura A, Moreira PI, Lee HG, Zhu X, Castellani RJ, Smith MA, Perry G Neuronal death is a common feature in neurodegenerative diseases including Alzheimer disease (AD) and Parkinson disease (PD). This occurs over years, not the minutes of classically defined apoptosis, and neurons show both responses of apoptosis and regeneration, evidenced by accumulated oxidative insult and attempts at cell cycle re-entry. There is recent evidence suggesting that several known gene mutations in causing familial AD (amyloid beta protein precursor, presenilin-1, or presenilin-2 gene) and familial PD (Parkin, PINK-1, or DJ-1 gene) are associated with increased oxidative stress. Also, several known genetic (e.g. Apolipoprotein Eepsilon4 variant) and environmental (e.g. metals or pesticides exp... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=1483612 Sat, 01 Dec 2007 05:00:00 +0100 1483612 http://www.medworm.com/index.php?rid=1483611&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18220781%26dopt%3DAbstract Authors: Unterberger U, Voigtländer T Prion diseases are rare fatal neurodegenerative disorders that may either occur sporadically, or be inherited or infectiously acquired in humans. Irrespective of etiology, they can be transmitted to other individuals, this fact being responsible for the public attention prion diseases have received especially since the nineteen nineties, when a new variant of Creutzfeldt-Jakob disease linked to the consumption of prion contaminated beef occurred for the first time in Great Britain. The infectious particle, termed prion, is presumably composed exclusively of a misfolded, partially protease-resistant conformer (PrP(Sc)) of a normal cell surface protein, the cellular prion protein (PrP(C)). The pathogenesis of prion diseases comprises entry, spre... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=1483611 Sat, 01 Dec 2007 05:00:00 +0100 1483611 http://www.medworm.com/index.php?rid=1483623&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18045158%26dopt%3DAbstract Authors: Galvan V, Bredesen DE The function of neurogenesis in the adult brain is still unknown. Interventions such as environmental enrichment and exercise impinge on neurogenesis, suggesting that the process is regulated by experience. Conversely, a role for neurogenesis in learning has been proposed through 'cellular plasticity', a process akin to synaptic plasticity but operating at the network level. Although neurogenesis is stimulated by acute injury, and possibly by neurodegenerative processes such as Alzheimer's disease (AD), it does not suffice to restore function. While the role and direction of change in the neurogenic response at different stages of AD is still a matter of debate, it is possible that a deficit in neurogenesis may contribute to AD pathogenesis since at least... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=1483623 Mon, 01 Oct 2007 04:00:00 +0100 1483623 http://www.medworm.com/index.php?rid=1483622&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18045159%26dopt%3DAbstract Authors: Banasr M, Duman RS Structural and morphological changes in limbic brain regions are associated with depression, chronic stress and antidepressant treatment, and increasing evidence supports the hypothesis that dysregulation of cell proliferation contributes to these effects. We review the morphological alterations observed in two brain regions implicated in mood disorders, the prefrontal cortex and hippocampus, and discuss the similarities and differences of the cellular consequences of chronic stress. We briefly discuss the proposed mechanisms implicated in neuroplasticity impairments that result from stress and that contribute to mood disorders, with a particular interest in adult neurogenesis and gliogenesis. This information has contributed to novel antidepressant medicati... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=1483622 Mon, 01 Oct 2007 04:00:00 +0100 1483622 http://www.medworm.com/index.php?rid=1483621&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18045160%26dopt%3DAbstract Authors: Greenberg DA Stroke stimulates neurogenesis in select regions of the adult brain, and the newborn neurons that result can migrate to areas of ischemic injury, where they may have the capacity to enhance brain recovery. These observations suggest that stroke-induced neurogenesis may contribute to endogenous brain repair after stroke, and that the mechanisms that underlie neurogenesis may represent potential therapeutic targets. Alternatively, transplantation of exogenously derived neural cells might also be an approach to the treatment of stroke. PMID: 18045160 [PubMed - indexed for MEDLINE] (Source: CNS and Neurological Disorders Drug Targets) CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=1483621 Mon, 01 Oct 2007 04:00:00 +0100 1483621 http://www.medworm.com/index.php?rid=1483620&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18045161%26dopt%3DAbstract Authors: Arias-Carrión O, Freundlieb N, Oertel WH, Höglinger GU Parkinson's disease is a neurodegenerative disorder characterized by a progressive neuronal loss affecting preferentially the dopaminergic neurons of the nigrostriatal projection. Transplantation of fetal dopaminergic precursor cells has provided the proof of principle that a cell replacement therapy can ameliorate clinical symptoms in affected patients. Recent years have provided evidence for the existence of neural stem cells with the potential to produce new neurons, particularly of a dopaminergic phenotype, in the adult mammalian brain. Such stem cells have been identified in so called neurogenic brain areas, where neurogenesis is constitutively ongoing, but also in primarily non-neurogenic areas, such as the... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=1483620 Mon, 01 Oct 2007 04:00:00 +0100 1483620 http://www.medworm.com/index.php?rid=1483619&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18045162%26dopt%3DAbstract Authors: Jordan JD, Ma DK, Ming GL, Song H Neural stem cells are present throughout life and continuously give rise to new neurons and glia cells in the mammalian central nervous system. Accumulating evidence suggests essential roles of micro-environments, or niches, in supporting active neurogenesis from endogenous neural stem cells within restricted regions of the adult brain. These neurogenic niches also regulate different steps of adult neurogenesis in response to physiological and pathological stimulations. Recent studies have identified several cellular niche components, including endothelial cells, astroglia, ependymal cells, immature progeny of NSCs and mature neurons. In this review, we discuss identified niche signals from these cellular components in regulating different ste... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=1483619 Mon, 01 Oct 2007 04:00:00 +0100 1483619 http://www.medworm.com/index.php?rid=1483618&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18045163%26dopt%3DAbstract Authors: Kuruba R, Shetty AK The dentate gyrus, a region of the hippocampal formation, displays the highest level of plasticity in the brain and exhibits neurogenesis all through life. Dentate neurogenesis, believed to be essential for learning and memory function, responds to physiological stimuli as well as pathological situations. The role of dentate neurogenesis in the pathophysiology of temporal lobe epilepsy (TLE) has received increased attention lately because of its disparate response in the early and chronic stages of the disease. Acute seizures or status epilepticus immensely enhance dentate neurogenesis and lead to an aberrant migration of newly born neurons into the dentate hilus and the formation of epileptogenic circuitry in the injured hippocampus. Conversely, spontaneou... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=1483618 Mon, 01 Oct 2007 04:00:00 +0100 1483618 http://www.medworm.com/index.php?rid=1483617&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18045164%26dopt%3DAbstract Authors: Vaidya VA, Vadodaria KC, Jha S The evidence that new neuron addition takes place in the mammalian brain throughout adult life has dramatically altered our perspective of the potential for plasticity in the adult CNS. Although several recent reports suggest a latent neurogenic capacity in multiple brain regions, the two major neurogenic niches that retain the ability to generate substantial numbers of new neurons in adult life are the subventricular zone (SVZ) lining the lateral ventricles and the subgranular zone (SGZ) in the hippocampal formation. The discovery of adult neurogenesis has also unveiled a novel therapeutic target for the repair of damaged neuronal circuits. In this regard, understanding the endogenous mechanisms that regulate adult neurogenesis holds promise bot... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=1483617 Mon, 01 Oct 2007 04:00:00 +0100 1483617 http://www.medworm.com/index.php?rid=1483633&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17691977%26dopt%3DAbstract Authors: Agosti RM Serotonin was the first neurotransmitter believed to be involved in cephalic pain transfer forward to the cortex, but the precise mechanism was confirmed only after sumatriptan, a 5-HT(1B/1D0) high affinity agonist, was introduced in the acute treatment of migraine. Although very efficient for migraine relief, activation of 5-HT(1B) receptor may also cause vasoconstriction outside brain, within the heart arteries for example. Unlike 5-HT(1B), the 5-HT(1D) receptor is not located in vascular tissues but exclusively within neuronal, but high affinity agonists for 5-HT(1D) failed to prove clinical significance in randomized trials. The recent clone of 5-HT(1F) receptor together with data showing that sumatriptan exerts high affinity for this receptor subtype generated h... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=1483633 Wed, 01 Aug 2007 04:00:00 +0100 1483633 http://www.medworm.com/index.php?rid=1483632&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17691978%26dopt%3DAbstract Authors: Ashina M The pathophysiology of tension-type headache is still far from clear, although recent advances in basic and clinical research have increased our knowledge about mechanisms underlying this disorder. Experimental studies suggest that increased excitability of the CNS generated by repetitive and sustained pericranial myofascial input may be responsible for transformation of episodic tension-type headache into chronic form. Future studies should focus on the identification of the source of peripheral nociception in patients with tension-type headache and the development of more effective and specific treatment modalities. PMID: 17691978 [PubMed - indexed for MEDLINE] (Source: CNS and Neurological Disorders Drug Targets) CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=1483632 Wed, 01 Aug 2007 04:00:00 +0100 1483632 http://www.medworm.com/index.php?rid=1483631&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17691979%26dopt%3DAbstract Authors: Edvinsson L, Petersen KA Primary headaches are among the most prevalent neurological disorders, afflicting up to 16% of the adult population. Associated pain originates from intracranial blood vessels that are innervated by sensory nerves storing several neurotransmitters. In primary headaches, there is a clear association between the headache and the release of calcitonin gene-related peptide (CGRP) but not with other neuronal messengers. The specific purpose of this review is to describe CGRP in the human cranial circulation and to elucidate a possible role for a specific antagonist in the treatment of primary headaches. Acute treatment by administration of a triptan (5-HT(1B/1D) agonist) results in alleviation of the headache and normalization of the elevated CGRP level. Th... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=1483631 Wed, 01 Aug 2007 04:00:00 +0100 1483631 http://www.medworm.com/index.php?rid=1483630&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17691980%26dopt%3DAbstract Authors: Puppe A, Limmroth V Within the last decades significant progress has been made in the understanding of the underlying pathophysiological mechanisms of migraine. There is a general agreement now that migraine is not only a vascular phenomenon but also a genetically determined heterogenic ion-channelopathy resulting in cortical-spreading-depression-like events, the temporary impairment of antinociceptive structures of the brainstem and the activation of the trigeminal-vascular system. The development and use of drugs targeting ion-channels and subsequently reducing cortical excitability appears as a promising avenue for both the acute treatment of migraine and migraine prevention. This review summarizes the current knowledge and evidence for GABAergic drugs in the treatment of m... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=1483630 Wed, 01 Aug 2007 04:00:00 +0100 1483630 http://www.medworm.com/index.php?rid=1483629&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17691981%26dopt%3DAbstract Authors: Vikelis M, Mitsikostas DD Glutamate (Glu) is the principal excitatory neurotransmitter in the central nervous system. Its receptors are classified into ionotropic receptors, which are ion channels and include NMDA, AMPA and kainate receptors, named after the agonists that selectively bind to them, and metabotropic receptors, which are G-protein coupled receptors. The trigeminal system is considered to play a key role in migraine pathophysiology, trafficking pain signals from the head and face to the trigeminal nucleus caudalis. The role of glutamate in the pathophysiology of migraine is implicated by data from animal and human studies. Animal studies include experiments of cortical spreading depression, studies of c-fos protein expression in trigeminal nucleus caudalis, studie... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=1483629 Wed, 01 Aug 2007 04:00:00 +0100 1483629 http://www.medworm.com/index.php?rid=1483628&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17691982%26dopt%3DAbstract Authors: Neeb L, Reuter U The potent vasodilatator and messenger molecule nitric oxide (NO) is believed to play a key role in migraine pathogenesis. NO donors such as glyceryl trinitrate (GTN) can cause headache. Infusion of GTN leads to a migraine attack in migraineurs with a latency of 4 to 6 hours. In this review we focus in the role of nitric oxide and the transcription factor nuclear factor-kappaB (NF-kappaB) in migraine pathophysiology in humans and animal models. NO is involved in pain transmission, hyperalgesia, chronic pain, inflammation and central sensitization mostly in a cyclic guanosinemono-phosphate (cGMP) dependent way. We aim to illustrate how NO is implicated in the induction of a migraine attack in migraineurs and how experimental animal models may help to elucidate ... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=1483628 Wed, 01 Aug 2007 04:00:00 +0100 1483628 http://www.medworm.com/index.php?rid=1483627&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17691983%26dopt%3DAbstract Authors: Stone JM, Pilowsky LS Since the discovery of the first antipsychotic drug, chlorpromazine, in the early 1950s, all effective antipsychotic drugs have been found to share the common property of dopamine D2 receptor antagonism. There has been some suggestion that simple D2 receptor antagonism may not confer optimal antipsychotic efficacy. Currently available antipsychotic drugs leave many symptoms of the illness untreated and cause unacceptable side effects. Recent research in schizophrenia suggests a number of potential new non-D2 targets for pharmacotherapy including glutamate, acetylcholine and serotonin neurotransmitter systems. This review summarises the main neurochemical theories of schizophrenia, and, in the light of these, examines possible therapeutic targets for new a... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=1483627 Wed, 01 Aug 2007 04:00:00 +0100 1483627 http://www.medworm.com/index.php?rid=1483626&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17691984%26dopt%3DAbstract Authors: Chen LW, Wang YQ, Wei LC, Shi M, Chan YS Parkinson's disease (PD) is a common and debilitating degenerative disease resulting from massive degenerative loss of dopamine neurons, particularly in the substantia nigra. The most classic therapy for PD is levodopa administration, but the efficacy of levodopa treatment declines as the disease progresses. The neuroprotective strategies to rescue nigral dopamine neurons from progressive death are currently being explored, and among them, the Chinese herbs and herbal extracts have shown potential clinical benefit in attenuating the progression of PD in human beings. Growing studies have indicated that a range of Chinese herbs or herbal extracts such as green tea polyphenols or catechins, panax ginseng and ginsenoside, ginkgo biloba and... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=1483626 Wed, 01 Aug 2007 04:00:00 +0100 1483626 http://www.medworm.com/index.php?rid=1483625&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17691985%26dopt%3DAbstract Authors: Schmeer C, Kretz A, Isenmann S 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, generically termed statins, are widely prescribed for their cholesterol-lowering properties. In addition to lipid-lowering properties, statins have pleiotropic effects including anti-inflammatory, anti-apoptotic, and antiproliferative effects. Recently, data from experimental and observational studies have indicated that statins could also become a treatment option for diseases of the central nervous system (CNS). Many neurodegenerative diseases particularly affect the retina and other ocular structures and are the cause for blindness. This review, focused on recent clinical and experimental data, discusses known and putative mechanisms of statin actions underlying neuroprotect... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=1483625 Wed, 01 Aug 2007 04:00:00 +0100 1483625 http://www.medworm.com/index.php?rid=1483624&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17691986%26dopt%3DAbstract Authors: Sierra-Paredes G, Sierra-Marcuño G Epilepsy is a neurological disorder in which normal brain function is disrupted as a consequence of intensive and synchronous burst activity from neuron assemblies. Epilepsies result from long-lasting plastic changes in the brain affecting neurotransmitter release, the properties of receptors and channels, synaptic reorganization and astrocyte activity. There is considerable evidence for alterations in glutamatergic and GABAergic synaptic transmission in the origin of the paroxysmal depolarization shifts that initiate epileptic activity. However, recent studies on non-synaptic transmission, receptor mobility and glia-neuron signaling pathways suggest that extrasynaptic GABA and glutamate receptors may play an important role in seizure in... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=1483624 Wed, 01 Aug 2007 04:00:00 +0100 1483624 http://www.medworm.com/index.php?rid=1483639&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17511613%26dopt%3DAbstract Authors: Duman RS, Kehne JH PMID: 17511613 [PubMed - indexed for MEDLINE] (Source: CNS and Neurological Disorders Drug Targets) CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=1483639 Fri, 01 Jun 2007 04:00:00 +0100 1483639 http://www.medworm.com/index.php?rid=1483638&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17511614%26dopt%3DAbstract Authors: Kehne JH The present review focuses on the corticotropin releasing factor type 1 (CRF(1)) receptor as a novel target for treating depression, anxiety and other stress-related disorders. An organism's stress response system is a complex network of neuronal, endocrine and autonomic pathways which has evolved to provide adaptive reactions to severe environmental and physiological stressors. The peptide CRF plays a critical role in the proper functioning of the stress response system through its actions on CRF(1) receptors located at multiple anatomical sites. Clinical data indicate that dysfunctions of the stress response system, expressed as excessive CRF activity and possible hyperstimulation of CRF(1) receptors, are present in a range of stress-related disorders, including dep... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=1483638 Fri, 01 Jun 2007 04:00:00 +0100 1483638 http://www.medworm.com/index.php?rid=1483637&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17511615%26dopt%3DAbstract Authors: Lu X, Sharkey L, Bartfai T Our present view that the mood disorders involve dysfunction of monoaminergic system is a result of important clinical and preclinical observations over the past 40 years. The therapeutic efficacy of drugs such as the tricyclic antidepressants (TCAs), monoamine oxidase inhibitors, selective serotonin reuptake inhibitors (SSRIs) and lately of SNRIs (serotonin and norepinephrine reuptake inhibitors) helped to shape our view that mood regulation involves the monoaminergic systems in some way. It is thus little surprising when the neuropeptide, galanin, is discovered to coexist with norepinephrine (NE) in locus coeruleus (LC) neurons and with serotonin (5-HT) in the dorsal raphe nucleus (DRN) neurons, a link between galanin mediated signaling and mood re... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=1483637 Fri, 01 Jun 2007 04:00:00 +0100 1483637 http://www.medworm.com/index.php?rid=1483636&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17511616%26dopt%3DAbstract Authors: Gould TD, Dow ER, O'Donnell KC, Chen G, Manji HK Regulation of complex signaling pathways plays a critical role in higher-order brain functions including the regulation of mood, cognition, appetite, sexual arousal, sleep patterns, and weight, all of which are altered in mood disorders, suggesting the involvement of signaling pathways in mood disorder pathogenesis and pathophysiology. Most existing medications used to treat mood disorders take many weeks to exert their full clinical effects, a fact which implicates changes in gene and protein expression, as well as neuroplasticity, in their mechanism of action. Modulation of signaling pathways has many downstream effects on gene expression and protein function, causing changes in synaptic function, plasticity, and response to v... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=1483636 Fri, 01 Jun 2007 04:00:00 +0100 1483636 http://www.medworm.com/index.php?rid=1483635&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17511617%26dopt%3DAbstract Authors: Drew MR, Hen R The dentate gyrus (DG) is one of only two brain structures known to retain the ability to produce new neurons in adulthood. The functional significance of adult neurogenesis in the DG is not yet well understood, but recent evidence has implicated adult neurogenesis in the etiology and treatment of depression. Elevated stress hormone levels, which are present in some depressed patients and can precipitate the onset of depression, reduce neurogenesis in animal models. Conversely, virtually all antidepressant treatments studied to date, including drugs of various classes, electroconvulsive therapy, and behavioral treatments, increase neurogenesis in the DG. We critically review this literature linking DG neurogenesis with depression, looking to both animal and huma... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=1483635 Fri, 01 Jun 2007 04:00:00 +0100 1483635 http://www.medworm.com/index.php?rid=1483634&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17511618%26dopt%3DAbstract Authors: Rajkowska G, Miguel-Hidalgo JJ Recent research has changed the perception of glia from being no more than silent supportive cells of neurons to being dynamic partners participating in brain metabolism and communication between neurons. This discovery of new glial functions coincides with growing evidence of the involvement of glia in the neuropathology of mood disorders. Unanticipated reductions in the density and number of glial cells are reported in fronto-limbic brain regions in major depression and bipolar illness. Moreover, age-dependent decreases in the density of glial fibrillary acidic protein (GFAP) - immunoreactive astrocytes and levels of GFAP protein are observed in the prefrontal cortex of younger depressed subjects. Since astrocytes participate in the uptake, met... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=1483634 Fri, 01 Jun 2007 04:00:00 +0100 1483634 http://www.medworm.com/index.php?rid=1483646&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17430146%26dopt%3DAbstract Authors: Duman RS, Kehne JH PMID: 17430146 [PubMed - indexed for MEDLINE] (Source: CNS and Neurological Disorders Drug Targets) CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=1483646 Sun, 01 Apr 2007 04:00:00 +0100 1483646 http://www.medworm.com/index.php?rid=1483645&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17430147%26dopt%3DAbstract Authors: Witkin JM, Marek GJ, Johnson BG, Schoepp DD Current treatments for depression are less than optimal in terms of onset of action, response and remission rates, and side-effect profiles. Glutamate is the major excitatory neurotransmitter controlling synaptic excitability and plasticity in most brain circuits, including limbic pathways involved in depression. Thus, drugs that target glutamate neuronal transmission offer novel approaches to treat depression. Recently, the NMDA receptor antagonist ketamine has demonstrated clinical efficacy in a randomized clinical trial of depressed patients. Metabotropic glutamate (mGlu) receptors function to regulate glutamate neuronal transmission by altering the release of neurotransmitter or modulating the post-synaptic responses to glutamate... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=1483645 Sun, 01 Apr 2007 04:00:00 +0100 1483645 http://www.medworm.com/index.php?rid=1483644&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17430148%26dopt%3DAbstract Authors: Pittenger C, Sanacora G, Krystal JH Ample evidence indicates that glutamate homeostasis and neurotransmission are disrupted in major depressive disorder; but the nature of this disruption and the mechanisms by which it contributes to the syndrome are unclear. Likewise, the effect of existing antidepressants on glutamate is unclear, as is the potential of drugs directly targeting glutamatergic neurotransmission to act as novel antidepressant medications. These are areas of active research. Here we review current knowledge of the contribution of the NMDA receptor, one of the several types of glutamate receptor, to depression and its treatment. Several lines of evidence, in humans and in animal models, support the contention that neurotransmission via the NMDA receptor is dysregu... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=1483644 Sun, 01 Apr 2007 04:00:00 +0100 1483644 http://www.medworm.com/index.php?rid=1483643&cid=s_37004_13_f&fid=37004&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17430149%26dopt%3DAbstract Authors: Bleakman D, Alt A, Witkin JM There is an increasing body of evidence implicating a role for alpha-amino-3-hydroxy-5-methyl-4 isoxazoleproprionic acid (AMPA) receptors in major depression and in the actions of antidepressant drugs. Alterations in AMPA receptors and other ionotropic glutamate receptors have been reported in depression, and following antidepressant treatment. Compounds which augment signaling through AMPA receptors (AMPA receptor potentiators) exhibit antidepressant-like behavioral effects in animal models, and produce neuronal effects similar to those produced by currently available antidepressants, including neurotrophin induction and increases in hippocampal progenitor cell proliferation. Additionally, the antidepressant fluoxetine has been found to alter AMPA... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=1483643 Sun, 01 Apr 2007 04:00:00 +0100 1483643