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Mitochondria as a Therapeutic Target in Alzheimer's Disease and Diabetes.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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...
Source: CNS and Neurological Disorders Drug Targets - August 27, 2009 Category: Drugs & Pharmacology Authors: Moreira PI, Cardoso SM, Pereira CM, Santos MS, Oliveira CR Tags: CNS Neurol Disord Drug Targets Source Type: journals

Glutamate Receptors as Therapeutic Targets for Parkinson's Disease.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 mod...
Source: CNS and Neurological Disorders Drug Targets - August 27, 2009 Category: Drugs & Pharmacology Authors: Johnson KA, Conn PJ, Niswender CM Tags: CNS Neurol Disord Drug Targets Source Type: journals

Can Sigma-1 Receptor Agonist Fluvoxamine Prevent Schizophrenia?Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 antidepress...
Source: CNS and Neurological Disorders Drug Targets - August 27, 2009 Category: Drugs & Pharmacology Authors: Hashimoto K Tags: CNS Neurol Disord Drug Targets Source Type: journals

Aptamers as Innovative Diagnostic and Therapeutic Agents in the Central Nervous System.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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...
Source: CNS and Neurological Disorders Drug Targets - August 27, 2009 Category: Drugs & Pharmacology Authors: de Franciscis V, Esposito CL, Catuogno S, Cellai L, Cerchia L Tags: CNS Neurol Disord Drug Targets Source Type: journals

Beneficial and Adverse Effects of Molecularly Targeted Therapies for Acute Promyelocytic Leukemia in Central Nervous System.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 re...
Source: CNS and Neurological Disorders Drug Targets - August 27, 2009 Category: Drugs & Pharmacology Authors: Nagai S, Takahashi T, Kurokawa M Tags: CNS Neurol Disord Drug Targets Source Type: journals

High Dose Immunoglobulin (IVIG) May Reduce the Incidence of Langerhans Cell Histiocytosis (LCH)-Associated Central Nervous System Involvement.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 tre...
Source: CNS and Neurological Disorders Drug Targets - August 27, 2009 Category: Drugs & Pharmacology Authors: Imashuku S Tags: CNS Neurol Disord Drug Targets Source Type: journals

An Historical Perspective on Efforts to Treat Transmissible Spongiform Encephalopathy.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 cou...
Source: CNS and Neurological Disorders Drug Targets - August 27, 2009 Category: Drugs & Pharmacology Authors: Brown P Tags: CNS Neurol Disord Drug Targets Source Type: journals

Neuroinflammation in Prion Diseases: Concepts and Targets for Therapeutic Intervention.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 cytotoxi...
Source: CNS and Neurological Disorders Drug Targets - August 27, 2009 Category: Drugs & Pharmacology Authors: Riemer C, Gültner S, Heise I, Holtkamp N, Baier M Tags: CNS Neurol Disord Drug Targets Source Type: journals

Using Non-Pharmacological Approaches for CJD Patient and Family Support As Provided by the CJD Foundation and CJD Insight.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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)
Source: CNS and Neurological Disorders Drug Targets - August 27, 2009 Category: Drugs & Pharmacology Authors: Kranitz FJ, Simpson DM Tags: CNS Neurol Disord Drug Targets Source Type: journals

Cross Currents in Protein Misfolding Disorders: Interactions and Therapy.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 mole...
Source: CNS and Neurological Disorders Drug Targets - August 27, 2009 Category: Drugs & Pharmacology Authors: Morales R, Green KM, Soto C Tags: CNS Neurol Disord Drug Targets Source Type: journals

Complex Polyamines: Unique Prion Disaggregating Compounds.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 ...
Source: CNS and Neurological Disorders Drug Targets - August 27, 2009 Category: Drugs & Pharmacology Authors: Supattapone S, Piro JR, Rees JR Tags: CNS Neurol Disord Drug Targets Source Type: journals

Psychotropic Medications and the Treatment of Human Prion Diseases.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 prio...
Source: CNS and Neurological Disorders Drug Targets - August 27, 2009 Category: Drugs & Pharmacology Authors: Appleby BS Tags: CNS Neurol Disord Drug Targets Source Type: journals

RNAi for the Treatment of Prion Disease: A Window for Intervention in Neurodegeneration?Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 t...
Source: CNS and Neurological Disorders Drug Targets - August 27, 2009 Category: Drugs & Pharmacology Authors: White MD, Mallucci GR Tags: CNS Neurol Disord Drug Targets Source Type: journals

The sleep-wake cycle, the hypocretin/orexin system and narcolepsy: advances from preclinical research to treatment.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
PMID: 19689304 [PubMed - in process] (Source: CNS and Neurological Disorders Drug Targets)
Source: CNS and Neurological Disorders Drug Targets - July 31, 2009 Category: Drugs & Pharmacology Authors: Arias-Carrión O, Bradbury M Tags: CNS Neurol Disord Drug Targets Source Type: journals

Sleep-inducing factors.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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...
Source: CNS and Neurological Disorders Drug Targets - July 31, 2009 Category: Drugs & Pharmacology Authors: García-García F, Acosta-Peña E, Venebra-Muñoz A, Murillo-Rodríguez E Tags: CNS Neurol Disord Drug Targets Source Type: journals

Mechanisms of sleep-wake cycle modulation.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 genera...
Source: CNS and Neurological Disorders Drug Targets - July 31, 2009 Category: Drugs & Pharmacology Authors: Murillo-Rodríguez E, Arias-Carrión O, Sanguino-Rodríguez K, González-Arias M, Haro R Tags: CNS Neurol Disord Drug Targets Source Type: journals

Neuroimaging of narcolepsy.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 i...
Source: CNS and Neurological Disorders Drug Targets - July 31, 2009 Category: Drugs & Pharmacology Authors: Dang-Vu TT, Desseilles M, Schwartz S, Maquet P Tags: CNS Neurol Disord Drug Targets Source Type: journals

REM sleep behavior disorder and narcolepsy.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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...
Source: CNS and Neurological Disorders Drug Targets - July 31, 2009 Category: Drugs & Pharmacology Authors: Billiard M Tags: CNS Neurol Disord Drug Targets Source Type: journals

The hypocretins and their role in narcolepsy.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 mean...
Source: CNS and Neurological Disorders Drug Targets - July 31, 2009 Category: Drugs & Pharmacology Authors: Kroeger D, de Lecea L Tags: CNS Neurol Disord Drug Targets Source Type: journals

Integrative physiology of orexins and orexin receptors.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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...
Source: CNS and Neurological Disorders Drug Targets - July 31, 2009 Category: Drugs & Pharmacology Authors: Mieda M, Sakurai T Tags: CNS Neurol Disord Drug Targets Source Type: journals

Animal models of narcolepsy.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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...
Source: CNS and Neurological Disorders Drug Targets - July 31, 2009 Category: Drugs & Pharmacology Authors: Chen L, Brown RE, McKenna JT, McCarley RW Tags: CNS Neurol Disord Drug Targets Source Type: journals

Cell transplantation: a future therapy for narcolepsy?Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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)
Source: CNS and Neurological Disorders Drug Targets - July 31, 2009 Category: Drugs & Pharmacology Authors: Arias-Carrión O, Murillo-Rodríguez E Tags: CNS Neurol Disord Drug Targets Source Type: journals

Treatment of multiple sclerosis.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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) ...
Source: CNS and Neurological Disorders Drug Targets - May 31, 2009 Category: Drugs & Pharmacology Authors: Anlar O Tags: CNS Neurol Disord Drug Targets Source Type: journals

Neuromodulators and therapeutic targets in neuropathic pain: from molecules to man.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 ...
Source: CNS and Neurological Disorders Drug Targets - May 31, 2009 Category: Drugs & Pharmacology Authors: Bermejo PE, Anciones B Tags: CNS Neurol Disord Drug Targets Source Type: journals

Antiangiogenic therapy for high-grade gliomas.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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)
Source: CNS and Neurological Disorders Drug Targets - May 31, 2009 Category: Drugs & Pharmacology Authors: Chamberlain MC, Raizer J Tags: CNS Neurol Disord Drug Targets Source Type: journals

Blood-brain barrier transport of drugs for the treatment of brain diseases.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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, v...
Source: CNS and Neurological Disorders Drug Targets - May 31, 2009 Category: Drugs & Pharmacology Authors: Gabathuler R Tags: CNS Neurol Disord Drug Targets Source Type: journals

Polymer-based drug delivery devices for neurological disorders.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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...
Source: CNS and Neurological Disorders Drug Targets - May 31, 2009 Category: Drugs & Pharmacology Authors: Halliday AJ, Cook MJ Tags: CNS Neurol Disord Drug Targets Source Type: journals

Neuroprotective effects of tetracyclines: molecular targets, animal models and human disease.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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, ...
Source: CNS and Neurological Disorders Drug Targets - May 31, 2009 Category: Drugs & Pharmacology Authors: Orsucci D, Calsolaro V, Mancuso M, Siciliano G Tags: CNS Neurol Disord Drug Targets Source Type: journals

Active and passive Abeta-immunotherapy: preclinical and clinical studies and future directions: part II.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
PMID: 19355929 [PubMed - in process] (Source: CNS and Neurological Disorders Drug Targets)
Source: CNS and Neurological Disorders Drug Targets - March 31, 2009 Category: Drugs & Pharmacology Authors: Cribbs DH, Agadjanyan MG Tags: CNS Neurol Disord Drug Targets Source Type: journals

Antibody responses, amyloid-beta peptide remnants and clinical effects of AN-1792 immunization in patients with AD in an interrupted trial.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 ...
Source: CNS and Neurological Disorders Drug Targets - March 31, 2009 Category: Drugs & Pharmacology Authors: Kokjohn TA, Roher AE Tags: CNS Neurol Disord Drug Targets Source Type: journals

Immunotherapy in a natural model of Abeta pathogenesis: the aging beagle.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 huma...
Source: CNS and Neurological Disorders Drug Targets - March 31, 2009 Category: Drugs & Pharmacology Authors: Vasilevko V, Head E Tags: CNS Neurol Disord Drug Targets Source Type: journals

Alternative Abeta immunotherapy approaches for Alzheimer's disease.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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, ...
Source: CNS and Neurological Disorders Drug Targets - March 31, 2009 Category: Drugs & Pharmacology Authors: Town T Tags: CNS Neurol Disord Drug Targets Source Type: journals

Rationale for peptide and DNA based epitope vaccines for Alzheimer's disease immunotherapy.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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...
Source: CNS and Neurological Disorders Drug Targets - March 31, 2009 Category: Drugs & Pharmacology Authors: Ghochikyan A Tags: CNS Neurol Disord Drug Targets Source Type: journals

Critical issues for successful immunotherapy in Alzheimer's disease: development of biomarkers and methods for early detection and intervention.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 ...
Source: CNS and Neurological Disorders Drug Targets - March 31, 2009 Category: Drugs & Pharmacology Authors: Tarawneh R, Holtzman DM Tags: CNS Neurol Disord Drug Targets Source Type: journals

AD vaccines: conclusions and future directions.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
PMID: 19355935 [PubMed - in process] (Source: CNS and Neurological Disorders Drug Targets)
Source: CNS and Neurological Disorders Drug Targets - March 31, 2009 Category: Drugs & Pharmacology Authors: Wisniewski T Tags: CNS Neurol Disord Drug Targets Source Type: journals

Active and passive abeta-immunotherapy: preclinical and clinical studies and future directions: part I.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
PMID: 19275632 [PubMed - in process] (Source: CNS and Neurological Disorders Drug Targets)
Source: CNS and Neurological Disorders Drug Targets - March 1, 2009 Category: Drugs & Pharmacology Authors: Agadjanyan MG, Cribbs DH Tags: CNS Neurol Disord Drug Targets Source Type: journals

The role of microglia in antibody-mediated clearance of amyloid-Beta from the brain.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 bindin...
Source: CNS and Neurological Disorders Drug Targets - March 1, 2009 Category: Drugs & Pharmacology Authors: Morgan D Tags: CNS Neurol Disord Drug Targets Source Type: journals

Clearance of amyloid-beta peptide across the blood-brain barrier: implication for therapies in Alzheimer's disease.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 decrease...
Source: CNS and Neurological Disorders Drug Targets - March 1, 2009 Category: Drugs & Pharmacology Authors: Deane R, Bell RD, Sagare A, Zlokovic BV Tags: CNS Neurol Disord Drug Targets Source Type: journals

Quantitative and mechanistic studies of abeta immunotherapy.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 imm...
Source: CNS and Neurological Disorders Drug Targets - March 1, 2009 Category: Drugs & Pharmacology Authors: Golde TE, Das P, Levites Y Tags: CNS Neurol Disord Drug Targets Source Type: journals

Immunotherapy, vascular pathology, and microhemorrhages in transgenic mice.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 am...
Source: CNS and Neurological Disorders Drug Targets - March 1, 2009 Category: Drugs & Pharmacology Authors: Wilcock DM, Colton CA Tags: CNS Neurol Disord Drug Targets Source Type: journals

Targeting generation of antibodies specific to conformational epitopes of amyloid beta-derived neurotoxins.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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, expl...
Source: CNS and Neurological Disorders Drug Targets - March 1, 2009 Category: Drugs & Pharmacology Authors: Lambert MP, Velasco PT, Viola KL, Klein WL Tags: CNS Neurol Disord Drug Targets Source Type: journals

Alzheimer's disease, ceramide, visfatin and NAD.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 [...
Source: CNS and Neurological Disorders Drug Targets - December 1, 2008 Category: Drugs & Pharmacology Authors: Adams JD Tags: CNS Neurol Disord Drug Targets Source Type: journals

Alzheimer's disease drug development: old problems require new priorities.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 d...
Source: CNS and Neurological Disorders Drug Targets - December 1, 2008 Category: Drugs & Pharmacology Authors: Becker RE, Greig NH Tags: CNS Neurol Disord Drug Targets Source Type: journals

The proNGF-p75NTR-sortilin signalling complex as new target for the therapeutic treatment of Parkinson's disease.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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, where...
Source: CNS and Neurological Disorders Drug Targets - December 1, 2008 Category: Drugs & Pharmacology Authors: Chen LW, Yung KK, Chan YS, Shum DK, Bolam JP Tags: CNS Neurol Disord Drug Targets Source Type: journals

Central sensitisation phenomena in primary headaches: overview of a preventive therapeutic approach.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 frequ...
Source: CNS and Neurological Disorders Drug Targets - December 1, 2008 Category: Drugs & Pharmacology Authors: de Tommaso M, Sardaro M, Vecchio E, Serpino C, Stasi M, Ranieri M Tags: CNS Neurol Disord Drug Targets Source Type: journals

NF-kappaB, a potential therapeutic target for the treatment of multiple sclerosis.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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. immunos...
Source: CNS and Neurological Disorders Drug Targets - December 1, 2008 Category: Drugs & Pharmacology Authors: Yan J, Greer JM Tags: CNS Neurol Disord Drug Targets Source Type: journals

Drug addiction and brain targets: from preclinical research to pharmacotherapy.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
PMID: 19128198 [PubMed - in process] (Source: CNS and Neurological Disorders Drug Targets)
Source: CNS and Neurological Disorders Drug Targets - November 1, 2008 Category: Drugs & Pharmacology Authors: Rahman S Tags: CNS Neurol Disord Drug Targets Source Type: journals

Role of the dopamine transporter in the action of psychostimulants, nicotine, and other drugs of abuse.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 ...
Source: CNS and Neurological Disorders Drug Targets - November 1, 2008 Category: Drugs & Pharmacology Authors: Zhu J, Reith ME Tags: CNS Neurol Disord Drug Targets Source Type: journals

Selective antagonism at dopamine D3 receptors as a target for drug addiction pharmacotherapy: a review of preclinical evidence.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 behavio...
Source: CNS and Neurological Disorders Drug Targets - November 1, 2008 Category: Drugs & Pharmacology Authors: Heidbreder C Tags: CNS Neurol Disord Drug Targets Source Type: journals

Neuronal nicotinic receptors as brain targets for pharmacotherapy of drug addiction.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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...
Source: CNS and Neurological Disorders Drug Targets - November 1, 2008 Category: Drugs & Pharmacology Authors: Rahman S, López-Hernández GY, Corrigall WA, Papke RL Tags: CNS Neurol Disord Drug Targets Source Type: journals