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. Wed, 08 Feb 2012 14:04:06 +0100 http://www.medworm.com/index.php?rid=5579950&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%3D22229308%26dopt%3DAbstract Interception of Cocaine by Enzyme or Antibody Delivered with Viral Gene Transfer: A Novel Strategy for Preventing Relapse in Recovering Drug Users. CNS Neurol Disord Drug Targets. 2012 Jan 10; Authors: Brimijoin S Abstract Recent progress in enzyme engineering has led to versions of human butyrylcholinesterase (BChE) that hydrolyze cocaine efficiently in plasma, reduce concentrations reaching reward neurocircuity in the brain, and weaken behavioral responses to this drug. Along with enzyme advances, increasingly avid anti-cocaine antibodies and potent anti-cocaine vaccines have also been developed. Here we review these developments and consider the potential advantages along with the risks of delivering drug-intercepting proteins via gene transfer approaches to treat cocain... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=5579950 Tue, 10 Jan 2012 05:00:00 +0100 5579950 http://www.medworm.com/index.php?rid=5579949&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%3D22229309%26dopt%3DAbstract Magic Bullets and Arrows: Biologic Approaches to Treat Substance Use Disorders. CNS Neurol Disord Drug Targets. 2012 Jan 10; Authors: Skolnick P, Volkow ND PMID: 22229309 [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=5579949 Tue, 10 Jan 2012 05:00:00 +0100 5579949 http://www.medworm.com/index.php?rid=5579948&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%3D22229310%26dopt%3DAbstract Authors: Fahim RE, Kessler PD, Fuller SA, Kalnik MW Abstract Smoking is a global healthcare problem. Current smoking cessation rates using behavioral counseling and pharmacotherapeutic interventions have had modest success, with ~1:5 smokers remaining abstinent long-term. Nicotine vaccines are a new class of immunotherapeutics under development. It is believed that anti-nicotine antibodies arising from vaccination capture nicotine and prevent or reduce its entry into the brain, as the antibody-bound nicotine is too large to cross the blood-brain barrier. This in turn decreases the pleasurable effects of smoking, reducing or eliminating positive reinforcement, thereby making it easier for a smoker to quit smoking. Four vaccine candidates have advanced into clinical testing with mixe... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=5579948 Tue, 10 Jan 2012 05:00:00 +0100 5579948 http://www.medworm.com/index.php?rid=5579947&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%3D22229311%26dopt%3DAbstract Authors: Stowe GN, Schlosburg JE, Vendruscolo LF, Edwards S, Misra KK, Schulteis G, Zakhari JS, Koob GF, Janda KD Abstract Heroin addiction is a wide-reaching problem with a spectrum of damaging social consequences. Currently approved heroin addiction medications include drugs that bind at the same receptors (e.g. opioid receptors) occupied by heroin and/or its metabolites in the brain, but undesired side effects of these treatments, maintenance dependence and relapse to drug taking remains problematic. A vaccine capable of blocking heroin's effects could provide an economical, long-lasting and sustainable adjunct to heroin addiction therapy without the side effects associated with available treatment options. Heroin, however, presents a particularly challenging vaccine target as i... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=5579947 Tue, 10 Jan 2012 05:00:00 +0100 5579947 http://www.medworm.com/index.php?rid=5579946&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%3D22229312%26dopt%3DAbstract Authors: Koob G, Hicks M, Wee S, Rosenberg J, De BP, Kaminksy SM, Moreno A, Janda KD, Crystal RG Abstract The challenge in developing an anti-cocaine vaccine is that cocaine is a small molecule, invisible to the immune system. Leveraging the knowledge that adenovirus (Ad) capsid proteins are highly immunogenic in humans, we hypothesized that linking a cocaine hapten to Ad capsid proteins would elicit high-affinity, high-titer antibodies against cocaine, sufficient to sequester systemically administered cocaine and prevent access to the brain, thus suppressing cocaine-induced behaviors. Based on these concepts, we developed dAd5GNE, a disrupted E1ΓE3Γ serotype 5 Ad with GNE, a stable cocaine analog, covalently linked to the Ad capsid proteins. In pre-clinical studies, dAd5GNE evok... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=5579946 Tue, 10 Jan 2012 05:00:00 +0100 5579946 http://www.medworm.com/index.php?rid=5579945&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%3D22229313%26dopt%3DAbstract Authors: Shen X, Kosten TR Abstract Substance use disorders continue to be major medical and social problems worldwide. Current medications for substance use disorders have many limitations such as cost, availability, medication compliance, dependence, diversion of some to illicit use and relapse to addiction after discontinuing their use. Immunotherapies using either passive monoclonal antibodies or active vaccines have distinctly different mechanisms and therapeutic utility from small molecule approaches to treatment. They have great potential to help the patient achieve and sustain abstinence and have fewer of the above limitations. This review covers the cocaine vaccine development in detail and provides an overview of directions for developing anti-addiction vaccines against t... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=5579945 Tue, 10 Jan 2012 05:00:00 +0100 5579945 http://www.medworm.com/index.php?rid=5579944&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%3D22229314%26dopt%3DAbstract Authors: Owens SM, Atchley WT, Hambuchen MD, Peterson EC, Gentry WB Abstract Developing specific medications to treat (+)-methamphetamine (METH) addiction is a difficult challenge because METH has multiple sites of action that are intertwined with normal neurological function. As a result, no small molecule medication for the treatment of METH addiction has made it through the FDA clinical trials process. With the invention of a new generation of protein-based therapies, it is now possible to consider treating drug addiction by an entirely different approach. This new approach is based on the discovery of very high affinity anti-METH monoclonal antibodies (mAbs), which are non-addictive and antagonize METH effects from the blood stream without entering the brain. Due to a very long... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=5579944 Tue, 10 Jan 2012 05:00:00 +0100 5579944 http://www.medworm.com/index.php?rid=5579943&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%3D22229315%26dopt%3DAbstract Authors: Skaper SD PMID: 22229315 [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=5579943 Tue, 10 Jan 2012 05:00:00 +0100 5579943 http://www.medworm.com/index.php?rid=5579942&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%3D22229316%26dopt%3DAbstract Authors: Sharma A, Muresanu DF, Sharma HS Abstract In recent years, the incidence of heat stroke and associated brain pathology are increasing Worldwide. More than half of the world's population are living in areas associated with high heat environment especially during the summer season. Thus, new research is needed using novel drug targets to achieve neuroprotection in heat-induced brain pathology. Previous research from our laboratory showed that the pathophysiology of brain injuries following heat stroke are exacerbated by chronic intoxication of engineered nanoparticles of small sizes (50-60 nm) following identical heat exposure in rats. Interestingly, in nanoparticle-intoxicated animals the known neuroprotective agents in standard doses failed to induce effective neuroprotect... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=5579942 Tue, 10 Jan 2012 05:00:00 +0100 5579942 http://www.medworm.com/index.php?rid=5579941&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%3D22229317%26dopt%3DAbstract Authors: Sharma HS, Sharma A Abstract Human exposure to metal nanoparticles such as silver (Ag), copper (Cu) or aluminum (Al) is very common at work places involving automobile, aerospace industry, gun factories or defense related explosives makings. Additional sources of exposure to engineered nanoparticles affecting human health are chemical, electronics and communication industries. The nanoparticles (ca. 20 to 120 nm) easily enter the body through inhalation and are deposited into various tissues and organs including brain, for long periods of time. However, the pathophysiological reactions of nanoparticles in vivo on brain function are still not well known. Previous observations from our laboratory showed that engineered nanoparticles from Ag, Cu or Al (50-60 nm) when administ... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=5579941 Tue, 10 Jan 2012 05:00:00 +0100 5579941 http://www.medworm.com/index.php?rid=5579940&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%3D22229318%26dopt%3DAbstract Authors: Bonda DJ, Liu G, Men P, Perry G, Smith MA, Zhu X Abstract The pathological lesions typical of Alzheimer disease (AD) are sites of significant and abnormal metal accumulation. Metal chelation therapy, therefore, provides a very attractive therapeutic measure for the neuronal deterioration of AD, though its institution suffers fundamental deficiencies. Namely, chelating agents, which bind to and remove excess transition metals from the body, must penetrate the blood-brain barrier to instill any real effect on the oxidative damages caused by the presence of the metals in the brain. Despite many advances in chelation administration, however, this vital requirement remains therapeutically out of reach: the most effective chelators-i.e., those that have high affinity and specifi... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=5579940 Tue, 10 Jan 2012 05:00:00 +0100 5579940 http://www.medworm.com/index.php?rid=5579917&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%3D22229319%26dopt%3DAbstract Authors: Siklos L PMID: 22229319 [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=5579917 Tue, 10 Jan 2012 05:00:00 +0100 5579917 http://www.medworm.com/index.php?rid=5579911&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%3D22229320%26dopt%3DAbstract Authors: Truini A, Biasiotta A, Di Stefano G, Cesa SL, Leone C, Cartoni C, Federico V, Petrucci MT, Cruccu G Abstract We assessed the effect of palmitoylethanolamide (PEA) on pain and nerve function in patients with chemotherapy-induced painful neuropathy, in 20 patients undergoing thalidomide and bortezomib treatment for multiple myeloma. All patients were evaluated before and after a two-month treatment with PEA 300 mg BID using pain and warmth thresholds; blinded examiners measured motor and sensory nerve fibre function and laser-evoked potentials. Although no variables returned to normal values, pain and all neurophysiological measures-assessing Aα, Aβ, and Aδ fibres- significantly improved (P < 0.05). In contrast, warmth thresholds, assessing unmyelinated afferents, rema... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=5579911 Tue, 10 Jan 2012 05:00:00 +0100 5579911 http://www.medworm.com/index.php?rid=5579904&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%3D22229321%26dopt%3DAbstract This study extends the elucidation of the kinetic approach of analysis and quantifying enzyme-substrate and enzyme-inhibitor interactions, which is crucial to bringing any drug from bench to bedside. The acyl pocket of human AChE was found to interact with CP through the amino acid residues Y70, Y121, W233, F288, F290, Y334, F408 and Y442, while the anionic sub-site of catalytic site (CAS) interacted with the ligand through residues W84, N85, G116, G117, Y121, S122, G123, L127, Y130, E198, Y334, H443 and G444. CP displayed variable docking poses with the peripheral anionic site (PAS) of human AChE. The findings of kinetic analysis were reinforced by the results of docking experiments. Both the applied approaches strongly indicate partial mixed type of inhibition pattern for the study enzym... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=5579904 Tue, 10 Jan 2012 05:00:00 +0100 5579904 http://www.medworm.com/index.php?rid=5579902&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%3D22229322%26dopt%3DAbstract This study demonstrates that assessment of C-peptide levels is a useful tool to monitor the progress of MetS among patients suffering from Type-2 DM and AD, as these disorders are intertwined to each other by common metabolic pathways. Assessment of C-peptide levels, along with HDL-C levels, in patients can be used to monitor insulin resistance. PMID: 22229322 [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=5579902 Tue, 10 Jan 2012 05:00:00 +0100 5579902 http://www.medworm.com/index.php?rid=5579899&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%3D22229323%26dopt%3DAbstract Authors: Lafuente JV, Sharma A, Patnaik R, Muresanu DF, Sharma HS Abstract Long term exposure of nanoparticles e.g., silica dust (SiO2) from desert environment, or engineered nanoparticles from metals viz., Cu, Al or Ag from industry, ammunition, military equipment and related products may lead to adverse effects on mental health. However, this is unclear whether these nanoparticles may further adversely affect human health in situation in cardiovascular or metabolic diseases e.g., hypertension or diabetes. It is quite likely that in diabetes or hypertension where the body immune system is already compromised will have much adverse effects following nanoparticles exposure on human health as compared to their exposure to healthy individuals. Previous experiments from our laboratory ... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=5579899 Tue, 10 Jan 2012 05:00:00 +0100 5579899 http://www.medworm.com/index.php?rid=5579882&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%3D22229324%26dopt%3DAbstract Authors: Menon PK, Muresanu DF, Sharma A, Mössler H, Sharma HS Abstract Spinal cord injury (SCI) is the world's most disastrous disease for which these is no effective treatment. Several studies suggest that nanoparticles could adversely influence the pathology of SCI and thereby alter the efficacy of many neuroprotective agents. Thus, there is an urgent need to find suitable therapeutic agents that could minimize cord pathology following trauma upon nanoparticle intoxication. Our laboratory has been engaged for the last 7 years in finding suitable therapeutic strategies that could equally reduce cord pathology in normal and in nanoparticle-treated animal models of SCI. We observed that engineered nanoparticles from metals e.g., aluminum, silver and copper (50-60 nm) when administ... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=5579882 Tue, 10 Jan 2012 05:00:00 +0100 5579882 http://www.medworm.com/index.php?rid=5579878&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%3D22229325%26dopt%3DAbstract Authors: Muresanu DF, Muresanu DF, Sharma A, Tian ZR, Smith MA, Sharma HS Abstract Nanoparticles from environment or through industrial sources could induce profound alteration in human health leading to often brain dysfunction. However, this is still unclear whether nanoparticles intoxication could also alter the physiological or pathological responses of additional brain injury, stress response or disease processes. Our military personals engaged in combat or peacekeeping operations are often exposed to several nanoparticles from the environment e.g., Ag, Cu, Si, C, Al from various sources. In addition, these military personal are often exposed to high environmental heat, gun explosion missile injury head or spinal trauma. Thus it is likely that additional CNS injury or stress in... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=5579878 Tue, 10 Jan 2012 05:00:00 +0100 5579878 http://www.medworm.com/index.php?rid=5579872&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%3D22229326%26dopt%3DAbstract This study aimed to investigate the acute modulatory effect of bromazepam, a benzodiazepine derivative drug, on alpha and beta bands (8-35Hz) in primary motor areas (M1) through event-related spectral perturbation (ERSP). Ten healthy subjects were submitted to a cross-over double-blind design. Subjects performed a visuomotor task where they had to identify rapidly the ball launched horizontally and catch it quickly, while electroencephalographic activity was acquired. We found a statistically significant difference on the time windows of 2920 ms for 13Hz in the electrodes C3 and Cz, and on the time window of 2000 ms for 18Hz in the electrodes C3, when compared the bromazepam and placebo conditions. We concluded that the acute effects of bromazepam provoked changes in information process in... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=5579872 Tue, 10 Jan 2012 05:00:00 +0100 5579872 http://www.medworm.com/index.php?rid=5579871&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%3D22229327%26dopt%3DAbstract Authors: Patruno A, Tabrez S, Amerio P, Pesce M, Vianale G, Franceschelli S, Grilli A, Kamal MA, Reale M Abstract Extremely low frequency electromagnetic fields (ELF-EMF) have been found to produce a variety of biological effects. These effects of ELF-EMF depend upon frequency, amplitude, and length of exposure, And are also related to intrinsic susceptibility and responsiveness of different cell types. Although the mechanism of this interaction is still obscure ELF-EMF can influence cell proliferation, differentiation, cell cycle, apoptosis, DNA replication and protein expression. The aim of this study was to estimate various kinetic constants of catalase, cytochrome P450 and inducible nitric oxide synthase in response to ELF-EMF exposure in human HaCaT and THP-1 cell lines. In or... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=5579871 Tue, 10 Jan 2012 05:00:00 +0100 5579871 http://www.medworm.com/index.php?rid=5579870&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%3D22229328%26dopt%3DAbstract Authors: Magalov SI, Hasanov NF, Azizova NX, Novruzov AN, Mustafayev ZB, Kazimov SA, Sultanov SS, Hasanov EN, Aliev G Abstract Epilepsy is a devastating neurological disorder in which those afflicted can gain benefit from specific treatments based on their genetics and geographic location. Currently the prevalence of epilepsy is estimated at 0.5-3% of the world-wide population, and is increasing in developing countries. In order to make more accurate assessments of the prevalence of epilepsy, we applied the capture-recapture method in a 12-month study of epilepsy in a population from the Sharur district of Nakhichevan Autonomous Republic, Azerbaijan with 114,451 people from sixty-nine villages and towns. The following methods were applied to determine epilepsy: Door To Door (DTD) s... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=5579870 Tue, 10 Jan 2012 05:00:00 +0100 5579870 http://www.medworm.com/index.php?rid=5331894&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%3D21999727%26dopt%3DAbstract Authors: Di Giovanni G PMID: 21999727 [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=5331894 Thu, 20 Oct 2011 15:50:10 +0100 5331894 http://www.medworm.com/index.php?rid=5331893&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%3D21999728%26dopt%3DAbstract Authors: Witkin JM PMID: 21999728 [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=5331893 Thu, 20 Oct 2011 15:49:41 +0100 5331893 http://www.medworm.com/index.php?rid=5331892&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%3D21999729%26dopt%3DAbstract Authors: Bernstein HG, Keilhoff G, Steiner J, Dobrowolny H, Bogerts B Abstract Schizophrenia is a devastating, chronic brain disorder afflicting about 1percent percent of the population. The etiology, neuropathology, and pathophysiology of schizophrenia remain elusive. Intense research has been conducted in order to identify specific biological markers of schizophrenia. The gas nitric oxide (NO) is an important signaling molecule involved in many cellular events that take place in the cardiovascular, immune and nervous systems of animals. This present review aims to show that NO and its metabolites play eminent roles in schizophrenia and have a significant influence on our understanding of the development, progression and, possibly, treatment of the disease. Special emphasis is giv... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=5331892 Thu, 20 Oct 2011 15:49:13 +0100 5331892 http://www.medworm.com/index.php?rid=5331891&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%3D21999730%26dopt%3DAbstract Authors: Banach M, Piskorska B, Czuczwar S, Borowicz K Abstract Nitric oxide (NO) plays a variety of physiological and pathological roles in mammalian cells. In the central nervous system NO may behave as a second messenger, neuromodulator and neurotransmitter, which may suggest an essential role of this gaseous molecule in epilepsy and epileptogenesis. The aim of this review is to survey the current literature in terms of experimental and clinical evidence of anti- or proconvulsive properties of NO and its implications in the anticonvulsive action of antiepileptic drugs. Up-to-date multiple NO synthase (NOS) inhibitors and donors of NO were used in a plethora of seizure models (e.g. electrically and pharmacologically-evoked convulsions, amygdala-kindled seizures). Reported results... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=5331891 Thu, 20 Oct 2011 15:48:41 +0100 5331891 http://www.medworm.com/index.php?rid=5331890&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%3D21999731%26dopt%3DAbstract Authors: Ap F, J S, Ma A, Pozo-Rodrigálvarez A, Martínez-Murillo R Abstract Gliomas, defined as tumors of glial origin, represent between 2-5 percent of all adult cancer and comprise the majority of the primary brain tumors. Infiltrating gliomas, with an incidence of more than 40percent of brain tumors, are the most common and destructive primary brain tumors for which conventional therapies have not significantly improved patient outcome. In fact, patients suffering from malignant gliomas have poor prognoses and the majority has local tumor recurrence after treatment. Tumor growth and spread of tumor cells depend basically upon angiogenesis and on functional abnormalities of tumor cells in the control of apoptosis, as they are paradigmatic for their intrinsic resistance to multi... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=5331890 Thu, 20 Oct 2011 15:48:12 +0100 5331890 http://www.medworm.com/index.php?rid=5331889&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%3D21999732%26dopt%3DAbstract Authors: Pierucci M, Galati S, Valentino M, Di Matteo V, Benigno A, Muscat R, Pitruzzella A, Di Giovanni G Abstract Several recent studies have emphasized a crucial role for the nitrergic system in movement control and the pathophysiology of the basal ganglia (BG). These observations are supported by anatomical evidence demonstrating the presence of nitric oxide synthase (NOS) in all the basal ganglia nuclei. In fact, nitrergic terminals have been reported to make synaptic contacts with both substantia nigra dopamine-containing neurons and their terminal areas such as the striatum, the globus pallidus and the subthalamus. These brain areas contain a high expression of nitric oxide (NO)-producing neurons, with the striatum having the greatest number, together with important NO affer... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=5331889 Thu, 20 Oct 2011 15:47:42 +0100 5331889 http://www.medworm.com/index.php?rid=5331888&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%3D21999733%26dopt%3DAbstract Authors: Siciliano R, Barone E, Calabrese V, Rispoli V, Butterfield D, Mancuso C Abstract Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by severe cognitive impairment due to neuronal death. Although the lost of cognitive function is the main problem for AD subjects, death occurs due to secondary issues such as concomitant infections, respiratory complications or multi-organ failure. Current drugs used in AD are acetylcholinesterase inhibitors and antagonists of the N-methyl-D-aspartate receptor. These drugs may only slightly improve cognitive functions but have only very limited impact on the clinical course of the disease. Over the last 5 years, new targets were identified and innovative drugs against AD have been designed and developed. Worthy... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=5331888 Thu, 20 Oct 2011 15:47:12 +0100 5331888 http://www.medworm.com/index.php?rid=5331887&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%3D21999734%26dopt%3DAbstract In conclusion, hydrophobic interactions play a major role in the appropriate positioning of CP within the 'acyl pocket' as well as 'catalytic site' of AChE to permit suitable orientation and allow docking. This information may aid the design of more potent and versatile AChE-inhibitors as pharmacologic tools and drugs to characterize and treat neurological disorders, and additionally provides a model whose value can be quantitatively assessed by X-ray crystallographic analysis of the AChE-CP three-dimensional structure. PMID: 21999734 [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=5331887 Thu, 20 Oct 2011 15:46:44 +0100 5331887 http://www.medworm.com/index.php?rid=5331886&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%3D21999735%26dopt%3DAbstract Authors: Foti Cuzzola V, Ciurleo R, Giacoppo S, Marino S, Bramanti P Abstract Neurodegenerative diseases are a group of chronic, progressive disorders characterized by the gradual loss of neurons in several areas of the central nervous system (CNS).Substantial evidence has documented a common inflammatory mechanism in neurodegeneration.It is known that classical anti-inflammatory agents, steroids and nonsteroidal anti-inflammatory drugs, have not played a major role in the management of CNS inflammatory conditions.This may be partly due to the natural compartmentation of the brain by the blood-brain barrier. Thus, there is much interest in developing novel anti-inflammatory drugs that may help to prevent or ameliorate CNS inflammation. Resveratrol (RSV) has received considerable at... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=5331886 Thu, 20 Oct 2011 15:46:13 +0100 5331886 http://www.medworm.com/index.php?rid=5331885&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%3D21999736%26dopt%3DAbstract Conclusion: Compared with placebo, nimodipine can significantly improve clinical outcomes, as assessed by self-formulated standards and Glasgow outcome scores, and it can significantly reduce the occurrence of symptomatic cerebral vasospasm and delayed neurological function deficits (all cases), as well as cerebral infarction, although the incidence rate of recurrent haemorrhage and adverse reactions is not significantly reduced by nimodipine. PMID: 21999736 [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=5331885 Thu, 20 Oct 2011 15:45:42 +0100 5331885 http://www.medworm.com/index.php?rid=5142463&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%3D21838668%26dopt%3DAbstract Authors: Gopurappilly R, Pal R, Mamidi MK, Dey S, Bhonde R, Das AK Abstract Stroke causes a devastating insult to the brain resulting in severe neurological deficits because of a massive loss of different neurons and glia. In the United States, stroke is the third leading cause of death. Stroke remains a significant clinical unmet condition, with only 3% of the ischemic patient population benefiting from current treatment modalities, such as the use of thrombolytic agents, which are often limited by a narrow therapeutic time window. However, regeneration of the brain after ischemic damage is still active days and even weeks after stroke occurs, which might provide a second window for treatment. Neurorestorative processes like neurogenesis, angiogenesis and synaptic plasticity lead ... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=5142463 Sun, 14 Aug 2011 23:00:00 +0100 5142463 http://www.medworm.com/index.php?rid=5142462&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%3D21838669%26dopt%3DAbstract Authors: Zecca C, Gobbi C Abstract The so called "chronic cerebrospinal venous insufficiency (CCSVI) theory" has recently emerged, supporting the concept of cerebrospinal venous drainage impairment as the cause of MS. Since the first publication on this topic with a claimed 100% specificity and sensitivity of the condition for MS diagnosis, CCSVI theory has generated a scientific and mass media debate with a great hope for the miracle of a new possible endovascular treatment of MS ("liberation procedure"). We critically summarize the available evidence on CCSVI discussing inconsistent and incomplete replication of the original results by different groups, methodological limits and potential therapeutic implications. We conclude that the available data are insufficient to establish ... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=5142462 Sun, 14 Aug 2011 23:00:00 +0100 5142462 http://www.medworm.com/index.php?rid=5142461&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%3D21838670%26dopt%3DAbstract Authors: Vallano A, Fernández-Dueñas V, Pedrós C, Arnau JM, Ciruela F Abstract Adenosine receptors are G protein-coupled receptors (GPCRs) that mediate the physiological functions of adenosine. In the central nervous system adenosine A2A receptors (A2ARs) are highly enriched in striatopallidal neurons where they form functional oligomeric complexes with other GPCRs such us the dopamine D2 receptor (D2R). Furthermore, it is assumed that the formation of balanced A2AR/D2R receptor oligomers are essential for correct striatal function as the allosteric receptor-receptor interactions established within the oligomer are needed for properly sensing adenosine and dopamine. Interestingly, A2AR activation reduces the affinity of striatal D2R for dopamine and the blockade of A2AR with spe... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=5142461 Sun, 14 Aug 2011 23:00:00 +0100 5142461 http://www.medworm.com/index.php?rid=5142460&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%3D21838671%26dopt%3DAbstract Authors: Danzer KM, McLean PJ Abstract One of the critical issues in Parkinson disease (PD) research is the identity of the specific toxic, pathogenic moiety. In PD, mutations in alpha-synuclein (alpha-syn) or multiplication of the SNCA gene encoding alpha-syn result in a phenotype of cellular inclusions, cell death, and brain dysfunction. While the historical point of view has been that the macroscopic aggregates containing alpha-syn are the toxic species, in the last several years evidence has emerged that suggests instead that smaller soluble species - likely oligomers containing misfolded alpha-syn - are actually the toxic moiety and that the fibrillar inclusions may even be a cellular detoxification pathway and less harmful. If soluble misfolded species of alpha-syn are the to... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=5142460 Sun, 14 Aug 2011 23:00:00 +0100 5142460 http://www.medworm.com/index.php?rid=5142459&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%3D21838672%26dopt%3DAbstract Authors: Ponce FA, Lozano AM Abstract There has been renewed interest in the surgical treatment of Parkinson's disease (PD) over the past 20 years. In the 1940's to 1960's many PD patients underwent neurosurgical procedures to ablate specific brain targets to alleviate tremor and, to a lesser extent, akinesia and rigidity. With the introduction of levodopa in the 1960s, and the realization of its striking benefits, surgical treatment of movement disorders virtually disappeared. With time, limitations and adverse effects associated with drug treatment became all too apparent. With complications associated with long-term drug treatment, particularly levodopa-induced motor fluctuations and dyskinesias, limiting therapeutic effectiveness in many patients, surgery has been reexamined to... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=5142459 Sun, 14 Aug 2011 23:00:00 +0100 5142459 http://www.medworm.com/index.php?rid=5142458&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%3D21838673%26dopt%3DAbstract Authors: Cookson MR PMID: 21838673 [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=5142458 Sun, 14 Aug 2011 23:00:00 +0100 5142458 http://www.medworm.com/index.php?rid=5142457&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%3D21838674%26dopt%3DAbstract Authors: Arias-Carrión O, Machado S, Paes F, Velasques B, Teixeira S, Cárdenas-Morales L, Ribeiro P, Nardi AE Abstract Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive procedure whereby a pulsed magnetic field stimulates electrical activity in the brain. Parkinson's disease (PD) is a neurodegenerative process characterized by numerous motor and nonmotor clinical manifestations for which effective, mechanism-based treatments remain elusive. Consequently, more advanced non-invasive therapeutic methods are required. A possible method of rehabilitation that may be effective and potentially viable for use in clinical practice is rTMS. Here, we focus on the basic foundation of rTMS, the main findings of rTMS from animal models, the effects of rTMS on sensorimotor i... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=5142457 Sun, 14 Aug 2011 23:00:00 +0100 5142457 http://www.medworm.com/index.php?rid=5142456&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%3D21838675%26dopt%3DAbstract Authors: Volonté C PMID: 21838675 [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=5142456 Sun, 14 Aug 2011 23:00:00 +0100 5142456 http://www.medworm.com/index.php?rid=5142455&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%3D21838676%26dopt%3DAbstract Authors: Mickiewicz AL, Kordower JH Abstract Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by motor dysfunction that occurs secondary to loss of dopaminergic neurons in the nigrostriatal pathway. Current pharmacotherapies focus on the replacement of lost dopamine to alleviate disease symptoms. However, over time this method of therapy loses effectiveness due to the continued death of dopaminergic neurons. Alternative strategies for the treatment of PD are aimed at modifying the disease state through the preservation of remaining dopamine neurons or even the regeneration of dopamine innervation through the use of neurotrophic factors. Neurotrophic factors are specialized proteins that can promote neuronal development, maintain neuronal health and... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=5142455 Sun, 14 Aug 2011 23:00:00 +0100 5142455 http://www.medworm.com/index.php?rid=5142454&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%3D21838677%26dopt%3DAbstract Authors: Cenci MA, Ohlin KE, Odin P Abstract Dyskinesia and motor fluctuations affect up to 90% of patients with Parkinson's disease (PD) within ten years of L-DOPA pharmacotherapy, and represent a major challenge to a successful clinical management of this disorder. There are currently two main treatment options for these complications, namely, deep brain electrical stimulation or continuous dopaminergic agonist infusion. The latter is achieved using either subcutaneous apomorphine infusion or intrajejunal L-DOPA infusion. Some patients also benefit from the antidyskinetic effect of amantadine as an adjunct to L-DOPA treatment. Ongoing research in animal models of PD aims at disovering additional, novel treatment options that can either prevent or reverse dyskinesia and motor fluc... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=5142454 Sun, 14 Aug 2011 23:00:00 +0100 5142454 http://www.medworm.com/index.php?rid=5142453&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%3D21838678%26dopt%3DAbstract Authors: Quik M, Bordia T, Huang L, Perez X Abstract A promising target for improved therapeutics in Parkinson's disease is the nicotinic acetylcholine receptor (nAChR). nAChRs are widely distributed throughout the brain, including the nigrostriatal system, and exert important modulatory effects on numerous behaviors. Accumulating evidence suggests that drugs such as nicotine that act at these sites may be of benefit for Parkinson's disease treatment. Recent work indicates that a potential novel therapeutic application is the use of nicotine to reduce levodopa-induced dyskinesias, a side effect of dopamine replacement therapy for Parkinson's disease. Several clinical trials also report that nicotine may diminish disease symptoms. Not only may nAChR drugs provide symptomatic improve... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=5142453 Sun, 14 Aug 2011 23:00:00 +0100 5142453 http://www.medworm.com/index.php?rid=5142452&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%3D21838679%26dopt%3DAbstract Authors: Vancraenenbroeck R, Lobbestael E, De Maeyer M, Baekelandt V, Taymans JM Abstract Intense research efforts are currently directed at elucidating the etiology of Parkinson's disease (PD). One approach that has begun to shed light on the PD pathogenic pathways is the identification of disease genes through genetic linkage or association studies. These studies have revealed that several kinases may be involved in PD, as some PD genes encode kinases themselves while other PD genes are found in the same cellular pathways as kinases. Two of these kinases stand out as potential drug targets for novel PD therapy, namely leucine rich repeat kinase 2 (LRRK2) and the alpha-synuclein (alpha-syn) phosphorylating polo-like kinase 2 (PLK2). Indeed, both alpha-syn and LRRK2 show genetic li... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=5142452 Sun, 14 Aug 2011 23:00:00 +0100 5142452 http://www.medworm.com/index.php?rid=4969018&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%3D21631400%26dopt%3DAbstract Authors: Jaggi AS, Singh N Neuropathic pain is a debilitating form of treatment resistant chronic pain and responds poorly to the clinically available therapies. Studies from animal models of neuropathic pain have led to understanding of its pathobiology which includes complex interrelated pathways leading to peripheral and central neuronal sensitization. Advancements in the elucidation of neuropathic pain mechanisms have revealed a number of key targets that have been hypothesized to modulate clinical status. The present review discusses these therapeutic targets including noradrenaline and 5-HT reuptake inhibitors; sodium, calcium and potassium channels; inhibitory and excitatory neurotransmitters; neuropeptides including bradykinin, tachykinin, cholecystokinin, neuropeptide Y, vasoa... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=4969018 Tue, 31 May 2011 23:00:00 +0100 4969018 http://www.medworm.com/index.php?rid=4969017&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%3D21631401%26dopt%3DAbstract Authors: Beg S, Samad A, Alam MI, Nazish I Most of the newly developed drugs fails to achieve sufficient bioavailability in to brain due to low water solubility and low permeability. Drug delivery systems are one method for achieving entry of molecules to their desired site of action within the body. Dendrimers are the customizable nanopolymers with uniform and well-defined particle size and shape. Dendrimers are of eminent interest for biomedical applications because of their ability to cross cell membranes. This potential pharmaceutical delivery system crosses the blood brain barrier (BBB) and other important target points. The high level of control over the dendritic architecture (size, branching density, surface functionality) make dendrimers ideal carriers in the field of brain dr... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=4969017 Tue, 31 May 2011 23:00:00 +0100 4969017 http://www.medworm.com/index.php?rid=4969016&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%3D21631402%26dopt%3DAbstract Authors: Capsoni S, Brandi R, Arisi I, D'Onofrio M, Cattaneo A The neurotrophin Nerve Growth Factor (NGF) is essential for the maintenance and differentiation of basal forebrain cholinergic neurons. Since basal forebrain cholinergic neurons represent one major neuronal population affected and progressively degenerating in Alzheimer's disease (AD), interest has grown for NGF as a potential therapeutic agent in neurodegenerative disorders linked to aging, particularly for AD. However, no evidence was available, to link, in a cause-effect manner, deficits in NGF signalling to the broader activation in the Alzheimer's cascade, besides cholinergic deficits. The phenotypic analysis of the AD11 anti-NGF transgenic mouse, obtained by the "neuroantibodies" phenotypic protein knock out strategy,... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=4969016 Tue, 31 May 2011 23:00:00 +0100 4969016 http://www.medworm.com/index.php?rid=4969015&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%3D21631403%26dopt%3DAbstract Authors: Paes F, Machado S, Arias-Carrión O, Velasques B, Teixeira S, Budde H, Cagy M, Piedade R, Ribeiro P, Huston JP, Sack AT, Nardi AE Unlike for depression, only few studies are available today investigating the therapeutic effects of repetitive transcranial magnetic stimulation (rTMS) for anxiety disorders. This review aims to provide information on the current research approaches and main findings regarding the therapeutic use of rTMS in the context of various anxiety disorders. Although positive results have frequently been reported in both open and randomized controlled studies, our review of all identified studies indicates that at present no conclusive evidence of the efficacy of rTMS for the treatment for anxiety disorders is provided. Several treatment parameters have been... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=4969015 Tue, 31 May 2011 23:00:00 +0100 4969015 http://www.medworm.com/index.php?rid=4969014&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%3D21631404%26dopt%3DAbstract Authors: Pizza V, Agresta A, D'Ac.o CW, Festa M, Capasso A Neuroinflammation is considered a chronic activation of the immune response in the central nervous system (CNS) in response to different injuries. This brain immune activation results in various events: circulating immune cells infiltrate the CNS; resident cells are activated; and pro-inflammatory mediators produced and released induce neuroinflammatory brain disease. The effect of immune diffusible mediators on synaptic plasticity might result in CNS dysfunction during neuroinflammatory brain diseases. The CNS dysfunction may induce several human pathological conditions associated with both cognitive impairment and a variable degree of neuroinflammation. Furthermore, age has a powerful effect on enhanced susceptibility to neur... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=4969014 Tue, 31 May 2011 23:00:00 +0100 4969014 http://www.medworm.com/index.php?rid=4969013&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%3D21631405%26dopt%3DAbstract Authors: Rahman S PMID: 21631405 [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=4969013 Tue, 31 May 2011 23:00:00 +0100 4969013 http://www.medworm.com/index.php?rid=4969012&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%3D21631406%26dopt%3DAbstract Authors: Pillarisetti S PMID: 21631406 [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=4969012 Tue, 31 May 2011 23:00:00 +0100 4969012 http://www.medworm.com/index.php?rid=4969011&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%3D21631407%26dopt%3DAbstract Authors: Talwar R, Potluri VK Cannabinoids are antinociceptive in animal models of acute pain, tissue injury and nerve injury induced nociception and act via their cognate receptors, cannabinoid receptor 1 and 2. This review examines the underlying biology of the endocannabinoids and behavioural, neurophysiological, neuroanatomical evidence supporting the notion of pain modulation by these ligands with a focus on the current evidence encompassing the pharmacological characterization of CB1 agonists in this therapy. Separating the psychotropic effects of CB1 agonists from their therapeutic benefits is the major challenge facing researchers in the field today and with the discovery of peripherally acting agonists there seems to be a ray of hope emerging for the diverse potential therapeu... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=4969011 Tue, 31 May 2011 23:00:00 +0100 4969011 http://www.medworm.com/index.php?rid=4969010&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%3D21631408%26dopt%3DAbstract This article comprehensively analyzes the consequences of nerve injury on the expression of peripheral opioid receptors and peptides, and the impact of these changes on opioid analgesia, critically discussing positive and negative findings. Further focus is on a dual character of immune responses in the control of painful neuropathies. PMID: 21631408 [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=4969010 Tue, 31 May 2011 23:00:00 +0100 4969010 http://www.medworm.com/index.php?rid=4969009&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%3D21631409%26dopt%3DAbstract Authors: Pillarisetti S Interleukin-1beta (IL-1beta) has been implicated in many inflammatory and autoimmune diseases. Its role in pain, however, is under-appreciated. This may in part be due to the challenges involved in approaching the target from a therapeutic stand point. The scope of this brief review is to understand the direct and indirect roles of IL-1beta in contributing to different pain states including inflammatory and neuropathic pain, and discuss approaches to block IL-1beta production or IL-1beta-receptor interactions. PMID: 21631409 [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=4969009 Tue, 31 May 2011 23:00:00 +0100 4969009 http://www.medworm.com/index.php?rid=4969008&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%3D21631410%26dopt%3DAbstract Authors: Khanna IK, Alexander CW Fatty acid amide hydrolase (FAAH) is responsible for hydrolysis of endocannabinoid, anandamide (AEA), and N-acyl ethanolamines such as palmitoylethanolamine (PEA) and N-oleoylethanolamide (OEA). Genetic deletion or pharmacological inactivation of FAAH shows site-specific elevation of AEA that plays a role in the modulation of pain and other neurodegenerative disorders. The review elaborates recent progress and current status of diverse structural classes of reversible and irreversible FAAH inhibitors. The discussion also addresses ligand-enzyme active site interactions and mechanism of enzyme inactivation, emerging approaches to novel FAAH inhibitors, and ongoing efforts to address gaps in therapeutic utility of FAAH inhibitors. PMID: 21631410 [PubM... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=4969008 Tue, 31 May 2011 23:00:00 +0100 4969008 http://www.medworm.com/index.php?rid=4969007&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%3D21631411%26dopt%3DAbstract Authors: Fischer BD Opioid analgesics are the most frequently prescribed medications for the treatment of moderate or severe pain; however, their use is constrained by unwanted side effects. One therapeutic approach used to improve the side effect profile of opioids is the administration of a second drug in an opioid-containing mixture. Preclinical studies designed to predict the therapeutic potential of novel opioid-containing drug combinations are currently underway, and must rely on quantitative methods to assess their interactive effects. In this manuscript, an overview of isobolographic analysis is presented along with recent advances in isobolographic theory pertaining to drugs that differ in efficacy and to the statistical analysis of dose-addition. Next, studies using these ana... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=4969007 Tue, 31 May 2011 23:00:00 +0100 4969007 http://www.medworm.com/index.php?rid=4822963&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%3D21495957%26dopt%3DAbstract Authors: Muresanu DF PMID: 21495957 [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=4822963 Sun, 17 Apr 2011 23:00:00 +0100 4822963 http://www.medworm.com/index.php?rid=4822962&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%3D21495958%26dopt%3DAbstract Authors: Chen LW PMID: 21495958 [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=4822962 Sun, 17 Apr 2011 23:00:00 +0100 4822962 http://www.medworm.com/index.php?rid=4822961&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%3D21495959%26dopt%3DAbstract The objectives of this review are to describe neurogenesis in the adult murine and human brain (with particular emphasis to morphological aspects of this process) and to determine to what extent it is affected in animal models of HD and in the human HD brain. Due to very limited evidence referring to the impact of striatal pathology of HD phenotype on the adult neurogenesis in the SEZ, some results gained from our studies on two rat models of HD, i.e. the neurotoxic lesion and transgenic HD rats, and on human HD brains are discussed. PMID: 21495959 [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=4822961 Sun, 17 Apr 2011 23:00:00 +0100 4822961 http://www.medworm.com/index.php?rid=4822960&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%3D21495960%26dopt%3DAbstract Authors: Tomaskovic-Crook E, Crook JM There is a renewed enthusiasm for the clinical translation of human embryonic stem (hES) cells. This is abetted by putative clinically-compliant strategies for hES cell maintenance and directed differentiation, greater understanding of and accessibility to cells through formal cell registries and centralized cell banking for distribution, the revised US government policy on funding hES cell research, and paradoxically the discovery of induced pluripotent stem (iPS) cells. Additionally, as we consider the constraints (practical and fiscal) of delivering cell therapies for global healthcare, the more efficient and economical application of allogeneic vs autologous treatments will bolster the clinical entry of hES cell derivatives. Neurodegenerative d... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=4822960 Sun, 17 Apr 2011 23:00:00 +0100 4822960 http://www.medworm.com/index.php?rid=4822959&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%3D21495961%26dopt%3DAbstract Authors: Abdel-Salam OM Alzheimer's disease (AD) is a progressive neurodegenerative disorder which impairs the memory and intellectual abilities of the affected individuals. Loss of episodic as well as semantic memory is an early and principal feature. The basal forebrain cholinergic system is the population of neurons most affected by the neurodegenerative process. Extracellular as well as intracellular deposition of beta-amyloid or Abeta (A) protein, intracellular formation of neurofibrillary tangles and neuronal loss are the neuropathological hallmarks of AD. In the last few years, hopes were raised that cell replacement therapy would provide cure by compensating the lost neuronal systems. Stem cells obtained from embryonic as well as adult tissue and grafted into the intact brain o... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=4822959 Sun, 17 Apr 2011 23:00:00 +0100 4822959 http://www.medworm.com/index.php?rid=4822958&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%3D21495962%26dopt%3DAbstract Authors: Chen LW, Kuang F, Wei LC, Ding YX, Yung KK, Chan YS Parkinson's disease (PD), a common degenerative disease in humans, is known to result from loss of dopamine neurons in the substantia nigra and is characterized by severe motor symptoms of tremor, rigidity, bradykinsia and postural instability. Although levodopa administration, surgical neural lesion, and deep brain stimulation have been shown to be effective in improving parkinsonian symptoms, cell replacement therapy such as transplantation of dopamine neurons or neural stem cells has shed new light on an alternative treatment strategy for PD. While the difficulty in securing donor dopamine neurons and the immuno-rejection of neural transplants largely hinder application of neural transplants in clinical treatment, induced ... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=4822958 Sun, 17 Apr 2011 23:00:00 +0100 4822958 http://www.medworm.com/index.php?rid=4822957&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%3D21495963%26dopt%3DAbstract Authors: Ding YX, Wei LC, Wang YZ, Cao R, Wang X, Chen LW Parkinson's disease (PD) is a severe deliberating neurological disease caused by progressive degenerative death of dopaminergic neurons in the substantia nigra of midbrain. While cell replacement strategy by transplantation of neural stem cells and inducement of dopaminergic neurons is recommended for the treatment of PD, understanding the differentiation mechanism and controlled proliferation of grafted stem cells remain major concerns in their clinical application. Here we review recent studies on molecular signaling pathways in regulation of Dopaminergic differentiation and proliferation of stem cells, particularly Wnt/beta-catenin signaling in stimulating formation of the dopaminergic phenotype, Notch signaling in inhibiting... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=4822957 Sun, 17 Apr 2011 23:00:00 +0100 4822957 http://www.medworm.com/index.php?rid=4822956&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%3D21495964%26dopt%3DAbstract Authors: Zhao J, Xu Q Parkinson's disease (PD) is a common neurodegenerative disease, characterized by a selective loss of midbrain Dopaminergic (DA) neurons. To address this problem, various types of stem cells that have potential to differentiate into DA neurons are being investigated as cellular therapies for PD, including cells derived from embryonic or adult donor tissue, and embryonic stem cells. These cell sources, however, have raised certain questions with regard to ethical and rejection issues. Recent progress in adult stems has further proved that the cells derived from adult tissue could be expanded and differentiated into DA precursor cells in vitro, and cell therapy with adult stem cells could produce a clear improvement for PD models. Using adult stem cells for clinic ap... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=4822956 Sun, 17 Apr 2011 23:00:00 +0100 4822956 http://www.medworm.com/index.php?rid=4822955&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%3D21495965%26dopt%3DAbstract Authors: Yuan TF, Arias-Carrión O Neurogenesis occurs in the adult brain in a constitutive manner under physiological circumstances within two regions: the dentate gyrus of the hippocampus and the subventricular zone of the lateral ventricles. In contrast to these two so-called neurogenic areas, other regions of the brain were considered to be primarily non-neurogenic in nature, implying that no new neurons were formed there under normal conditions. Recently, low proliferative activity was reported in the hypothalamus and the cell layers surrounding the third ventricle. This review summarizes recent evidence for adult neurogenesis in the hypothalamus, and points out the potential contributions of these new neurons to neural processing. We also discussed some technical considerations i... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=4822955 Sun, 17 Apr 2011 23:00:00 +0100 4822955 http://www.medworm.com/index.php?rid=4822954&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%3D21495966%26dopt%3DAbstract Authors: Osakada F, Takahashi M Embryonic stem (ES) cells are derived from the inner cell mass (ICM) of blastocyst stage embryos, while induced pluripotent stem (iPS) cells are generated from somatic cells through transient overexpression of defined transcription factors. When transplanted into a preimplantation embryo, ES cells and iPS cells can differentiate into any cell type, including germ cells. Moreover, they can grow in culture indefinitely while maintaining pluripotency. In vitro differentiation of ES cells and iPS cells recapitulates many aspects of in vivo embryogenesis. The acquisition of neural fates (neural induction) in ES cells can be controlled by bone morphogenetic protein (BMP), fibroblast growth factor (FGF), and Wnt signaling, while the production of specific neura... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=4822954 Sun, 17 Apr 2011 23:00:00 +0100 4822954 http://www.medworm.com/index.php?rid=4822953&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%3D21495967%26dopt%3DAbstract Authors: Cai S, Shea GK, Tsui AY, Chan YS, Shum DK Schwann cells are critically important for tissue repair, axonal regrowth and remyelination following injury to peripheral nerves. The absence of Schwann cells or an equivalent cell type in the central nervous system (CNS) may limit the regeneration capacity of the CNS. Mesenchymal stem cells (MSCs) have therefore been investigated for their potential to be induced to develop a Schwann cell phenotype. The methods for derivation of Schwann cell-like cells from MSCs and the benefits and limitations of each of these methods are presented in this review. Issues related to instability of the derived Schwann cell phenotype, apoptosis of derived cells in transplants, and the inability to predict with confidence how the cells will behave after... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=4822953 Sun, 17 Apr 2011 23:00:00 +0100 4822953 http://www.medworm.com/index.php?rid=4415430&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%3D21261586%26dopt%3DAbstract Authors: Skaper SD PMID: 21261586 [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=4415430 Mon, 31 Jan 2011 15:15:33 +0100 4415430 http://www.medworm.com/index.php?rid=4415429&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%3D21261587%26dopt%3DAbstract Authors: Choudary PV PMID: 21261587 [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=4415429 Mon, 31 Jan 2011 15:15:30 +0100 4415429 http://www.medworm.com/index.php?rid=4415428&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%3D21261588%26dopt%3DAbstract Authors: Skaper SD PMID: 21261588 [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=4415428 Tue, 25 Jan 2011 00:00:00 +0100 4415428 http://www.medworm.com/index.php?rid=4353696&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%3D21222620%26dopt%3DAbstract Authors: García-Horsman JA PMID: 21222620 [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=4353696 Tue, 11 Jan 2011 00:00:00 +0100 4353696 http://www.medworm.com/index.php?rid=4353695&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%3D21222621%26dopt%3DAbstract Authors: Van Elzen R, Lambeir AM Prolyl oligopeptidase (POP) belongs to a unique class of serine proteases. Based on extensive enzyme kinetic measurements it has become clear that POP acts in a multifaceted way. This is reflected in the complex behavior in different reaction conditions with different substrates. Also the typical structural architecture of POP, with the active site located at the interface of the catalytic domain and the beta-propeller domain, has instigated many researchers to speculate about the mechanism of functioning. The latest developments support the idea of extended conformational changes upon substrate binding. In this review the plethora of available information is assembled into a coherent and stepwise description of the structural composition of POP. In one... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=4353695 Tue, 11 Jan 2011 00:00:00 +0100 4353695 http://www.medworm.com/index.php?rid=4353694&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%3D21222622%26dopt%3DAbstract Authors: Tenorio-Laranga J, Männistö PT, García-Horsman JA Prolyl oligopeptidase (POP) is a serine protease that cleaves peptides shorter than 30-mer at the carboxyl side of an internal proline. POP has been proposed to be involved in some pathologies including mood disorders and neurodegenerative diseases. However, the physiological role of POP remains unknown. To validate POP as a drug target, it is essential to obtain a thorough understanding of its function in vivo. Identification of physiological substrates and products of POP is an important step towards this goal. Recent peptidomic studies have revealed some biological substrates of POP and have given information about the in vivo consequences of POP inhibition. The aim of this review it is to evaluate new advances in this re... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=4353694 Tue, 11 Jan 2011 00:00:00 +0100 4353694 http://www.medworm.com/index.php?rid=4353693&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%3D21222623%26dopt%3DAbstract Authors: Penttinen A, Tenorio-Laranga J, Siikanen A, Morawski M, Rossner S, García-Horsman JA Inhibitors of prolyl oligopeptidase have been reported to be neuroprotective, especially in memory loss caused by lesion or disease. This enzyme has also been implicated in neurodegeneration. Although it was initially thought that prolyl oligopeptidase functioned to directly control of neuropeptide levels, emerging evidence points out in part that this peptidase modulates peptides which in turn regulate inflammatory responses. Here we review the recent literature which indicates a direct involvement of prolyl oligopeptidase in several inflammatory diseases. Neuroinflammation generates neurotoxins with a relevant role in neurodegenerative diseases, and it is within this toxin generation where ... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=4353693 Tue, 11 Jan 2011 00:00:00 +0100 4353693 http://www.medworm.com/index.php?rid=4353692&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%3D21222624%26dopt%3DAbstract Authors: Lambeir AM Prolyl oligopeptidase (PO) interacts with alpha-syncline in vitro. It is a weak interaction that induces a nucleation prone conformation of alpha-synuclein. PO accelerates aggregation and fibril formation of alpha-syncline in a process that can be reversed by specific inhibitors and is also influenced by an impairing mutation in the PO active site. There is evidence that PO and alpha-synuclein also interact intracellularly, especially in conditions where the expression of alpha-synuclein is high. Specific PO inhibitors reduce the number of cells with alpha-synuclein inclusions in a cellular model of Parkinson's disease. If these interactions also exist in the human brain, PO may be a target for the treatment of Parkinson's disease and other synucleinopathies. Whethe... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=4353692 Tue, 11 Jan 2011 00:00:00 +0100 4353692 http://www.medworm.com/index.php?rid=4353691&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%3D21222625%26dopt%3DAbstract Authors: Harwood AJ Inhibition of prolyl oligopeptidase (PO) elevates inositol phosphate (IP) signalling and reduces cell sensitivity to lithium (Li+). This review discusses recent evidence that shows PO acts via the multiple inositol polyphosphate phosphatase (MIPP) to regulate gene expression. As a consequence, PO inhibition causes both a transient, rapid increase in I(1,4,5)P3 and a long-term elevation of IP signalling. This pathway is evolutionary conserved, being present in both the social amoeba Dictyostelium and human cell systems, and has potential implications for mental health. PMID: 21222625 [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=4353691 Tue, 11 Jan 2011 00:00:00 +0100 4353691 http://www.medworm.com/index.php?rid=4353690&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%3D21222626%26dopt%3DAbstract Authors: Rea D, Fülöp V Prolyl oligopeptidase or prolyl endopeptidase (PREP; EC 3.4.21.26) is an atypical serine protease that hydrolyses peptides and peptide hormones after proline in peptides up to around 30 residues long. Evidence suggests an involvement in learning and memory, and the enzyme is implicated in diseases including amnesia and depression. The first crystal structures determined, of the porcine enzyme, provided direct insight into the mechanisms of substrate size selectivity, substrate specificity, and catalysis. However in these structural studies the enzyme is in a closed state, even in the absence of ligand, leaving questions as to how substrates and products can enter and exit the enclosed central cavity that houses the active site. More recent crystal structures o... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=4353690 Tue, 11 Jan 2011 00:00:00 +0100 4353690 http://www.medworm.com/index.php?rid=4353689&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%3D21222627%26dopt%3DAbstract Authors: Boonen K, Régal L, Jaeken J, Creemers JW Deletion of the Prolyl Endopeptidase-like (PREPL) gene has been described in three contiguous gene deletion syndromes at the 2p21 locus and current developments in high resolution microarrays and whole genome sequencing will no doubt soon result in the identification of isolated PREPL deficiency. But by comparing the differences in phenotypes with the number of genes deleted, the contribution of PREPL deficiency can already be deduced. Homozygous or compound heterozygous loss of PREPL is predicted to cause neonatal hypotonia and severe feeding problems. Failure to thrive usually persists for several years, followed by a period of hyperphagia and excessive weight gain. Growth retardation is usually observed, which responds well to growt... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=4353689 Tue, 11 Jan 2011 00:00:00 +0100 4353689 http://www.medworm.com/index.php?rid=4353688&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%3D21222628%26dopt%3DAbstract Authors: Morawski M, Schulz I, Zeitschel U, Blosa M, Seeger G, Roßner S Prolyl endopeptidase (E.C. 3.4.21.26, PREP) also known as prolyl oligopeptidase is an enzyme which cleaves several peptides at the carboxyl side of proline residues. Since brain contains relatively large amounts of this enzyme and because of its substrate specificity it has been suggested to play a role in the metabolism of neuropeptides, acting both on their maturation and their degradation. The final step of neuropeptide processing occurs in the synaptic vesicles and degradation of most of these peptides takes place in the synaptic cleft. Thus, a localization of PREP in these cellular compartments appears to be feasible. Here we summarize recent data and provide novel evidence for the subcellular localization of... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=4353688 Tue, 11 Jan 2011 00:00:00 +0100 4353688 http://www.medworm.com/index.php?rid=4353687&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%3D21222629%26dopt%3DAbstract Authors: Peltonen I, Myöhänen TT, Männistö PT Prolyl oligopeptidase (POP), is an 80-kDa serine protease that hydrolyzes peptides smaller than 30-mer at the carboxyl side of an internal proline-residue. POP is commonly believed to cleave a number of neuropeptides claimed to be involved in learning, memory and mood. While the support to the neuropeptide cleavage theory has been declining, new data suggest novel functions for POP, e.g. as a regulator of protein secretion, alpha-synuclein aggregation and cell proliferation/differentiation. Intriguingly, many of these novel functions may not depend on the hydrolytic activity of POP. One of the new roles is an involvement of POP in neurotransmission. Indeed, POP has been associated with a variety of different neurotransmitters. According... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=4353687 Tue, 11 Jan 2011 00:00:00 +0100 4353687 http://www.medworm.com/index.php?rid=4353686&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%3D21222630%26dopt%3DAbstract Authors: Aliev G PMID: 21222630 [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=4353686 Tue, 11 Jan 2011 00:00:00 +0100 4353686 http://www.medworm.com/index.php?rid=4353685&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%3D21222631%26dopt%3DAbstract Authors: Palacios HH, Yendluri BB, Parvathaneni K, Shadlinski VB, Obrenovich ME, Leszek J, Gokhman D, Gąsiorowski K, Bragin V, Aliev G Age-related dementias such as Alzheimer disease (AD) have been linked to vascular disorders like hypertension, diabetes and atherosclerosis. These risk factors cause ischemia, inflammation, oxidative damage and consequently reperfusion, which is largely due to reactive oxygen species (ROS) that are believed to induce mitochondrial damage. At higher concentrations, ROS can cause cell injury and death which occurs during the aging process, where oxidative stress is incremented due to an accelerated generation of ROS and a gradual decline in cellular antioxidant defense mechanisms. Neuronal mitochondria are especially vulnerable to oxidative stress due to... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=4353685 Tue, 11 Jan 2011 00:00:00 +0100 4353685 http://www.medworm.com/index.php?rid=4353684&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%3D21222632%26dopt%3DAbstract Authors: Gasiorowski K, Lamer-Zarawska E, Leszek J, Parvathaneni K, Yendluri BB, Bach-Olszewska Z, Aliev G Flavonoids are natural, plant-derived compounds which exert diverse biological activities, alsovaluable neuroprotectiveactions within the brain and currently are intensively studied as agents able to modulate neuronal function and to prevent age-related neurodegeneration. Among them, flavones isolated from Scutellariabaicalensis root exhibit strong neuroprotectiveeffects on the brain and are not toxic in the broad range of tested doses. Their neuroprotective potential has been shown in both oxidative stress-induced and amyloid-beta and alpha-synuclein-induced neuronal death models. Baicalein, the main flavone present in Scutellariabaicalensis root, strongly inhibited aggregation o... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=4353684 Tue, 11 Jan 2011 00:00:00 +0100 4353684 http://www.medworm.com/index.php?rid=4353683&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%3D21222633%26dopt%3DAbstract Authors: Sieradzki A, Yendluri BB, Palacios HH, Parvathaneni K, Reddy VP, Obrenovich ME, Siorowski KG, Leszek J, Aliev G Recent evidence has associated the aberrant, proximal re-expression of various cell cycle control elements with neuronal cell vulnerability in Alzheimer's and Parkinson's diseases, as a common chronic neurodegeneration. This phenomenon associated with oncogenic transduction pathway activation has attracted the interest of scientists all over the world for a few years now. The purpose of this paper is to outline areas of research related to oncogenic factors or medicines in the context of potential applications for future treatment of the above mentioned chronic and, largely, incurable diseases. PMID: 21222633 [PubMed - as supplied by publisher] (Source: CNS and N... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=4353683 Tue, 11 Jan 2011 00:00:00 +0100 4353683 http://www.medworm.com/index.php?rid=4353682&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%3D21222634%26dopt%3DAbstract Authors: Simon D, Medina M, Avila J, Wandosell F Few targets for neuroprotection have been defined in Alzheimer's disease (AD). Recent data from the role of Wnt, insulin-like growth factor-1 and estradiol pathways in AD suggest some therapeutic targets for disease treatment, and have led us to evaluate the "common factors" in these pathways as further candidate targets. These data have led us to propose that glycogen synthase kinase-3 (GSK-3) inhibition appears to be a common feature of these pathways. Besides, considering that GSK-3 activation seems to be correlated with neurodegeneration, its selection as a relevant target appears obvious. The capacity of different GSK-3 inhibitors to prevent amyloid -peptide neurotoxicity and tau phosphorylation has been evaluated in order to develo... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=4353682 Tue, 11 Jan 2011 00:00:00 +0100 4353682 http://www.medworm.com/index.php?rid=4353681&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%3D21222635%26dopt%3DAbstract Authors: Galimberti D, Scarpini E The two major neuropathologic hallmarks of AD are extracellular amyloid beta (A ) plaques and intracellular neurofibrillary tangles (NFTs). A number of additional pathogenic mechanisms, possibly overlapping with A plaques and NFTs formation, have been described, including inflammation, oxidative damage, iron dysregulation, and alterations in cholesterol metabolism. In this review, all of these mechanisms will be discussed and treatments that are under development to interfere with these pathogenic steps will be presented. A primary goal of work in this area is identification of novel compounds that can block the course of the disease in early phases. For this reason they are currently termed "disease modifying" drugs. These drugs are designed to modify... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=4353681 Tue, 11 Jan 2011 00:00:00 +0100 4353681 http://www.medworm.com/index.php?rid=4353680&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%3D21226664%26dopt%3DAbstract Authors: Obrenovich ME, Li Y, Parvathaneni K, Yendluri BB, Palacios HH, Leszek J, Aliev G There is growing scientific agreement that antioxidants, particularly the polyphenolic forms, may help lower the incidence of disease, such as certain cancers, cardiovascular and neurodegenerative diseases, DNA damage, or even have anti-aging properties. On the other hand, questions remain as to whether some antioxidants or phytochemicals potentially could do more harm than good, as an increase in glycation-mediated protein damage (carbonyl stress) and some risk has been reported. Nevertheless, the quest for healthy aging has led to the use of antioxidants as a means to disrupt age-associated deterioration in physiological function, dysregulated metabolic processes or prevention of many age-relate... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=4353680 Tue, 11 Jan 2011 00:00:00 +0100 4353680 http://www.medworm.com/index.php?rid=4285431&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%3D21143138%26dopt%3DAbstract Authors: Hoozemans JJ, Veerhuis R, Rozemuller JM, Eikelenboom P Epidemiological studies suggest that systemic use of non-steroidal anti-inflammatory drugs (NSAIDs) can prevent or retard the development of Alzheimer's disease (AD). However, clinical trials investigating the effects of NSAIDs on AD progression have yielded mixed or inconclusive results. The aim of this review is to distinguish the role of inflammation and the molecular targets of NSAIDs in the different stages of AD pathology. AD brains are characterized by extracellular deposits of -amyloid protein and intraneuronal accumulation of hyperphosphorylated tau protein. Already in the early stages of AD pathology -amyloid protein deposits are associated with inflammatory proteins and microglia, the brain resident macrophages.... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=4285431 Tue, 14 Dec 2010 00:00:00 +0100 4285431 http://www.medworm.com/index.php?rid=4285430&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%3D21143139%26dopt%3DAbstract Authors: Skaper SD Under pathological conditions microglia (resident CNS immune cells) become activated, and produce reactive oxygen and nitrogen species and pro-inflammatory cytokines: molecules that can contribute to axon demyelination and neuron death. Because some microglia functions can exacerbate CNS disorders, including stroke, traumatic brain injury, progressive neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and multiple sclerosis, and several retinal diseases, controlling their activation might ameliorate immune-mediated CNS disorders. A growing body of evidence now points to ion channels on microglia as contributing to the above neuropathologies. For example, the ATP-gated P2X7 purinergic receptor cation channel is... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=4285430 Tue, 14 Dec 2010 00:00:00 +0100 4285430 http://www.medworm.com/index.php?rid=4285429&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%3D21143140%26dopt%3DAbstract Authors: Harris RA, Amor S The nervous system is a unique network of different cell types and comprises a variety of proteins, lipids, and carbohydrates that have an important interplay with all major organs in the body. Homeostatic regulation of nervous tissue turnover must be carefully controlled, taking into account interactions of the nervous, endocrine, and immune systems. Clinical conditions affecting the nervous system range from mild cognitive perturbations such as headache, to life-threatening acute courses such as meningitis and glioblastoma, and to chronic neurodegenerative diseases such as multiple sclerosis. One unifying feature in normal developmental or homeostatic functions and clinical dysfunctions within the nervous system is redox regulation, with an imbalance in oxi... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=4285429 Tue, 14 Dec 2010 00:00:00 +0100 4285429 http://www.medworm.com/index.php?rid=4285428&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%3D21143141%26dopt%3DAbstract Authors: Olah M, Biber K, Vinet J, Boddeke HW Microglia, the tissue macrophages of the brain, have under healthy conditions a resting phenotype that is characterized by a ramified morphology. With their fine processes microglia are continuously scanning their environment. Upon any homeostatic disturbance microglia rapidly change their phenotype and contribute to processes including inflammation, tissue remodeling, and neurogenesis. In this review, we will address functional phenotypes of microglia in diverse brain regions and phenotypes associated with neuroinflammation, neurogenesis, brain tumor homeostasis, and aging. PMID: 21143141 [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=4285428 Tue, 14 Dec 2010 00:00:00 +0100 4285428 http://www.medworm.com/index.php?rid=4285427&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%3D21143142%26dopt%3DAbstract Authors: Bajramovic JJ Innate immune responses in the central nervous system must be tightly regulated as unrestrained activation generates a chronic inflammatory environment that can contribute to neurodegeneration and autoimmunity. Microglia express a wide variety of receptors of the innate immune system and are competent responders to danger. Toll-like receptor-, NOD-like receptor- and RIG1-like receptormediated activation of microglia leads to the production of pro-inflammatory cytokines and to the upregulation of molecules implicated in activation of the adaptive immune system. Activated microglia are a characteristic feature of many neuroinflammatory disorders and they represent an attractive therapeutic target. This review describes the mechanisms that are at play to restrain mi... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=4285427 Tue, 14 Dec 2010 00:00:00 +0100 4285427 http://www.medworm.com/index.php?rid=4285426&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%3D21143143%26dopt%3DAbstract Authors: van Noort JM, van den Elsen PJ, van Horssen J, Geurts JJ, van der Valk P, Amor S For the development of novel central nervous system (CNS) drugs to promote neuroprotection, it is helpful to gain a betterunderstanding of natural neuroprotective phenomena. Microglia play key roles in endogenous neuroprotective pathways and their activation is a common theme in several neurodegenerative disorders. Yet, while it is widely appreciated that activated microglia can have neuroprotective qualities, their contribution to tissue destruction and neurodegeneration within the CNS is equally obvious. This apparent duality in microglial functions renders it difficult to determine whether microglial activation under certain conditions is something to counteract, or to support. Also, it is far ... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=4285426 Tue, 14 Dec 2010 00:00:00 +0100 4285426 http://www.medworm.com/index.php?rid=4285425&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%3D21143144%26dopt%3DAbstract Authors: Hoarau JJ, Krejbich-Trotot P, Jaffar-Bandjee MC, Das T, Thon-Hon GV, Kumar S, Neal JW, Gasque P Innate immunity is an arsenal of molecules and receptors expressed by professional phagocytes, glial cells and neurons and involved in host defence and clearance of toxic and dangerous cell debris. However, any uncontrolled innate immune responses within the central nervous system (CNS) are widely recognized as playing a major role in the development of autoimmune disorders and neurodegeneration, with multiple sclerosis (MS) and Alzheimer's diseases (AD) being primary examples. Critically, neuroimmune regulatory proteins (NIReg) may control the adverse immune responses in health and diseases. NIRegs are found mainly on neurons, glia, endothelia and ependymal cells and include GPI-an... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=4285425 Tue, 14 Dec 2010 00:00:00 +0100 4285425 http://www.medworm.com/index.php?rid=4285424&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%3D21143145%26dopt%3DAbstract Authors: Amor S PMID: 21143145 [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=4285424 Tue, 14 Dec 2010 00:00:00 +0100 4285424 http://www.medworm.com/index.php?rid=4082497&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%3D20942783%26dopt%3DAbstract Authors: Outeiro TF, Kazantsev AG PMID: 20942783 [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=4082497 Wed, 20 Oct 2010 03:40:46 +0100 4082497 http://www.medworm.com/index.php?rid=4082496&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%3D20942784%26dopt%3DAbstract Authors: Thevandavakkam MA, Schwarcz R, Muchowski PJ, Giorgini F Huntington's disease (HD) is an adult onset neurodegenerative disease caused by a polyglutamine expansion in the huntingtin protein Recent work has shown that perturbation of kynurenine pathway (KP) metabolism is a hallmark of HD pathology, and that changes in brain levels of KP metabolites may play a causative role in this disease. The KP contains three neuroactive metabolites, the neurotoxins 3-hydroxykynurenine (3-HK) and quinolinic acid (QUIN), and the neuroprotectant kynurenic acid (KYNA). In model systems in vitro and in vivo, 3-HK and QUIN have been shown to cause neurodegeneration via a combination of excitotoxic mechanisms and oxidative stress. Recent studies with HD patient samples and in HD model systems have s... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=4082496 Wed, 20 Oct 2010 03:40:43 +0100 4082496 http://www.medworm.com/index.php?rid=4082495&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%3D20942785%26dopt%3DAbstract Authors: Bosco DA, Landers JE Amyotrophic lateral sclerosis (ALS) is an incurable disease resulting from the deterioration of motor neurons. The onset of disease typically occurs in the fifth decade of life and progresses rapidly; death occurs for 75% of patients within 5 years. The only drug that is available to treat ALS is riluzole, which extends survival by just 2-3 months. Thus, new therapeutic directions are being sought to prolong the lifespan of ALS patients. Since the discovery of SOD1 as a genetic determinant of ALS in 1993, SOD1-models of ALS have been extensively employed for the development of ALS therapeutics. Novel genetic targets are now under investigation following the recent discoveries linking TDP-43, FUS/TLS, angiogenin, KIFAP3 and UNC13A to ALS. In this review, we... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=4082495 Wed, 20 Oct 2010 03:40:40 +0100 4082495 http://www.medworm.com/index.php?rid=4082494&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%3D20942786%26dopt%3DAbstract Authors: Costa J, Gomes C, de Carvalho M Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease of the motor system. The diagnosis is clinical, but additional investigations such as electromyography, transcranial magnetic stimulation and neuroimaging have demonstrated their usefulness in supporting diagnosis. Exhaustive research for the identification of molecular markers in the cerebrospinal fluid and plasma of ALS patients have been made; however, at present, there are no validated biomarkers for the disease. Between 5 to 10% of the ALS cases have a positive familial history, up to now eleven genes have been identified as associated with the disease. The most studied gene encodes for cupper, zinc superoxide dismutase enzyme. The identified abnormal genes potentially... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=4082494 Wed, 20 Oct 2010 03:40:36 +0100 4082494 http://www.medworm.com/index.php?rid=4082493&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%3D20942787%26dopt%3DAbstract Authors: Diógenes MJ, Outeiro TF Neurodegenerative disorders are devastating human diseases that include Parkinson's, Huntington's, Alzheimer's, amyotrophic lateral sclerosis, and the frontal temporal dementias. Although the clinical manifestations of these disorders have been known for quite some time, our understanding of the molecular underpinnings is only starting to emerge. Protein misfolding and aggregation is a common hallmark among these diseases, and produce a number of cellular and functional alterations. The loss of dopaminergic neurons in the substantia nigra justified the use of dopaminergic therapies in patients. However, these strategies do not appear to confer disease-modifying effects, and do not prevent progression. The idea that neurotrophic factors might promote ce... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=4082493 Wed, 20 Oct 2010 03:40:33 +0100 4082493 http://www.medworm.com/index.php?rid=4082492&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%3D20942788%26dopt%3DAbstract Authors: Kalia SK, Kalia LV, McLean PJ Parkinson's disease is a neurodegenerative movement disorder that is caused, in part, by the loss of dopaminergic neurons within the substantia nigra pars compacta of the basal ganglia. The presence of intracellular protein aggregates, known as Lewy bodies and Lewy neurites, within the surviving nigral neurons is the defining neuropathological feature of the disease. Accordingly, the identification of specific genes mutated in families with Parkinson's disease and of genetic susceptibility variants for idiopathic Parkinson's disease has implicated abnormalities in proteostasis, or the handling and elimination of misfolded proteins, in the pathogenesis of this neurodegenerative disorder. Protein folding and the refolding of misfolded proteins are r... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=4082492 Wed, 20 Oct 2010 03:40:29 +0100 4082492 http://www.medworm.com/index.php?rid=4082491&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%3D20942789%26dopt%3DAbstract Authors: Badiola N, Suárez-Calvet M, Lleó A Tauopathies are neurodegenerative diseases characterized by insoluble hyperphosphorylated deposits of the microtubuleassociated protein tau in the central nervous system. In these disorders, tau is believed to cause neurodegeneration and neuronal loss due to the loss of function of the normal protein, and/or the gain of toxic properties by generating multimeric species. The obstacles found in amyloid-based therapies in Alzheimer's disease, the most common tauopathy, have stimulated the search for alternative targets, including tau. In this article, we review the strategies aimed at reducing tau phosphorylation and aggregation as a target for drug intervention in tauopathies. PMID: 20942789 [PubMed - as supplied by publisher] (Source: CN... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=4082491 Wed, 20 Oct 2010 03:40:26 +0100 4082491 http://www.medworm.com/index.php?rid=4082490&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%3D20942790%26dopt%3DAbstract Authors: da Cruz E Silva OA, Henriques AG, Timóteo SC, Domingues S, da Cruz E Silva EF One of the most important contributions to our understanding of neurodegenerative diseases in the last decade has been the demonstration that several disorders have a common biochemical cause, involving aggregation and deposition of abnormal proteins. Abnormal protein deposition leads to neuronal degeneration with consequences to impaired brain function. Protein deposition can be extracellular (beta-amyloid peptide (Abeta), prion protein) or intracellular (Tau, alpha-synuclein, huntingtin). Individuals with Alzheimer's disease (AD) exhibit extracellular senile plaques (SPs) of aggregated Abeta and intracellular neurofibrillary tangles that contain hyperphosphorylated Tau protein (NFTs), and also an ... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=4082490 Wed, 20 Oct 2010 03:40:22 +0100 4082490 http://www.medworm.com/index.php?rid=4082489&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%3D20942791%26dopt%3DAbstract Authors: Xilouri M, Stefanis L The autophagy-lysosomal pathway is a major proteolytic pathway that in mammalian systems mainly comprises of macroautophagy and chaperone-mediated autophagy. The former is relatively non-selective and involves bulk degradation of proteins and organelles, whereas the latter is selective for certain cytosolic proteins. These autophagy pathways are important in development, differentiation, cellular remodeling and survival during nutrient starvation. Autophagy is crucial for neuronal homeostasis and acts as a local housekeeping process, since neurons are post-mitotic cells and require effective protein degradation to prevent accumulation of toxic aggregates. A growing body of evidence now suggests that dysfunction of autophagy causes accumulation of abnormal... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=4082489 Wed, 20 Oct 2010 03:40:19 +0100 4082489 http://www.medworm.com/index.php?rid=4082488&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%3D20942792%26dopt%3DAbstract Authors: Pruss RM Target-directed drug design, although a conceptually rational approach, is only one strategy for drug discovery. In the case of neurodegenerative diseases where molecular targets and disease mechanisms are unknown, even when specific genes are known to trigger the disease, phenotypic screening offers another approach. This review describes the establishment of phenotypic screening assays using primary neurons subjected to a disease-relevant pathophysiological stress and measuring the most important functional outcome, survival. Although a challenge both to screening teams to reproducibly produce the cells and chemists to interpret structure-activity relationships, such systems have historically identified or produced effective drugs. The primary screening assay is onl... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=4082488 Wed, 20 Oct 2010 03:40:15 +0100 4082488 http://www.medworm.com/index.php?rid=4082487&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%3D20942793%26dopt%3DAbstract Authors: Viana RJ, Fonseca MB, Ramalho RM, Nunes AF, Rodrigues CM Neurodegenerative diseases trigger neuronal cell death by a variety of endogenous suicide pathways. Although cell death may occur through highly heterogeneous processes, specific cell organelles and stress sensors have shown promise as potential therapeutic targets. The plasma membrane senses stress through residing receptors, which can directly or indirectly activate apoptosis. Importantly, several events involved in neuronal death also affect mitochondria homeostasis, leading to calcium uptake, opening of the permeability transition pore, and release of apoptogenic factors. In addition, nuclear DNA damage triggers cell death, where p53 is activated to modulate the expression of selected apoptosis target genes. Signalin... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=4082487 Wed, 20 Oct 2010 03:40:11 +0100 4082487 http://www.medworm.com/index.php?rid=4082486&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%3D20942794%26dopt%3DAbstract Authors: Borovecki F, Habek M Genomic blood biomarkers hold great promise for development of novel clinical and therapeutic approaches in patients with neurodegenerative diseases. Such biomarkers could prove invaluable in early disease diagnosis, monitoring of disease progression, or assessment of response to therapy. More importantly, they could be helpful in search for disease-modifying new therapies which are very much needed in modern approaches to treatment of neurodegenerative diseases, serving as surrogate endpoints in clinical trials. However, when performing expression profiling experiments aimed at discovery of new biomarker genes, standard operating procedures regarding sample collection, microarray methodology, and statistical analysis need to be fully developed and strictl... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=4082486 Wed, 20 Oct 2010 03:40:07 +0100 4082486 http://www.medworm.com/index.php?rid=4016073&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%3D20874694%26dopt%3DAbstract This article will review the current understanding of these underlying mechanisms and the research being carried with homocysteine as a core molecule. PMID: 20874694 [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=4016073 Tue, 28 Sep 2010 23:00:00 +0100 4016073 http://www.medworm.com/index.php?rid=4016072&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%3D20874695%26dopt%3DAbstract Authors: Manoonkitiwongsa PS Therapeutic angiogenesis is a novel treatment for ischemic stroke, and vascular endothelial growth factor (VEGF) is a key angiogenic and neuroprotective pharmacological candidate for therapy. However, the greatest challenge of preclinical studies is demonstrating that VEGF-based therapeutic angiogenesis is safe and effective for ischemic stroke patients. This review presents the following crucial questions which must first be answered by preclinical studies before VEGF-based therapeutic angiogenesis advances to human stroke trials, (1) Does angiogenesis induced by VEGF monotherapy promote neuroprotection or further damage the nervous tissue? (2) Does angiogenesis by VEGF in combination with other agents (combination therapy) promote greater neuroprotection ... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=4016072 Tue, 28 Sep 2010 23:00:00 +0100 4016072 http://www.medworm.com/index.php?rid=4016071&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%3D20874696%26dopt%3DAbstract Authors: Tang B, Qu Y, Wang D, Mu D Hypoxia/ischemia brain damage (HIBD) is one of the most common central nervous system insults in newborns. Brain repair following HIBD is closely associated with cellular processes such as cell survival, angiogenesis, and neurogenesis. In recent years, many studies have suggested that ginsenoside Rg1, one of the major active ingredients of ginseng, may increase neural viability, promote angiogenesis, and induce neurogenesis. However, there are few reports on roles of Rg1 in HIBD repair, and the mechanisms involved are unclear. Recently, a Chinese drug consisting of Rg1 has been shown to be a potential regulator of hypoxia-inducible factor-1 expression in HIBD. Since it has been shown that HIF-1 is a key transcription factor involved in the neuroprote... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=4016071 Tue, 28 Sep 2010 23:00:00 +0100 4016071 http://www.medworm.com/index.php?rid=4016070&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%3D20874697%26dopt%3DAbstract Authors: Tsartsalis S, Panagopoulos PK, Mironidou-Tzouveleki M The treatment of Alzheimer's disease is undoubtedly one of the greatest challenges of modern medicine and pharmacology. Affecting millions of people, Alzheimer's disease has become a major social problem. Several theories have been proposed to account for its pathogenesis. Possibly, the "amyloid cascade hypothesis" is the dominant one. However, the "inflammation hypothesis" also contributes to the pathogenesis of the disease. Thus, this study intends to describe the role of neuroinflammation in Alzheimer's disease, regarding its cellular and molecular components, and to examine if the use of non-steroidal anti-inflammatory drugs could be an effective "weapon" in the battle against it. PMID: 20874697 [PubMed - as supplie... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=4016070 Tue, 28 Sep 2010 23:00:00 +0100 4016070 http://www.medworm.com/index.php?rid=4016069&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%3D20874698%26dopt%3DAbstract We present recent studies on meningococcal disease with focus on the pathophysiology caused by bacterial virulence factors and the host immune responses. The bacterial outer membrane lipopolysaccharide and non-lipopolysaccharide components are related to meningococcal adhesion and invasion, while the host immune reactions propagate inflammation and neurodegeneration. Hence, bacterium-host interactions are key determinants of the clinical course and risk of fatal outcome. Accordingly, successful treatment of severe meningococcal disease requires not only antibiotics but also adjuvants targeting the released endotoxins and the host immune/inflammatory responses. This review highlights the most recent data and current knowledge on molecular mechanisms of meningococcal disease and explains how... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=4016069 Tue, 28 Sep 2010 23:00:00 +0100 4016069 http://www.medworm.com/index.php?rid=4016068&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%3D20874699%26dopt%3DAbstract Authors: De Filippis D, Cipriano M, Esposito G, Scuderi C, Steardo L, Iuvone T Recently, a pivotal role for neuroinflammation in the pathogenesis of several neurodegenerative diseases has been recognized. Once activated, glial cells produce pathological amounts of neurotoxic substances driving neurodegeneration into chronic progression through a self-propagating cycle. Nevertheless, mounting evidence suggests that also angiogenesis may importantly contribute to neurodegeneration, since activated glial cells may release also pro-angiogenic factors. A deregulation of the balance between pro- and anti-angiogenic mediators has been reported in in vivo and in vitro models of neuroinflammation. Indeed, in Alzheimer's disease brain, a significant increase in the expression of pro-angiogenic g... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=4016068 Tue, 28 Sep 2010 23:00:00 +0100 4016068 http://www.medworm.com/index.php?rid=4016067&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%3D20874700%26dopt%3DAbstract Authors: Archinti M, Britto M, Eden G, Furlan F, Murphy R, Degryse B The urokinase receptor (uPAR) is a multifunctional glycosylphosphatidylinositol-anchored protein that regulates important processes such as gene expression, cell proliferation, adhesion, migration, invasion, and metastasis. uPAR is an essential component of the plasminogen activation cascade, a protease receptor that binds the urokinase-type plasminogen activator. uPAR is also an adhesionmodulating receptor, and a signalling receptor transmitting signals to the cell through lateral interactions with a wide array of membrane receptors. Altogether, the external ligands and membrane-bound partners of uPAR constitute a rich uPAR interactome. Recently, a new ligand of uPAR has been identified as the SRPX2 protein which is ... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=4016067 Tue, 28 Sep 2010 23:00:00 +0100 4016067 http://www.medworm.com/index.php?rid=4016066&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%3D20874701%26dopt%3DAbstract Authors: Campos HC, da Rocha MD, Viegas FP, Nicastro PC, Fossaluzza PC, Fraga CA, Barreiro EJ, Viegas C The present review is part II in a series (part I focuses on Parkinson's Disease) that addresses the value of natural product chemistry in the discovery of medicines for the treatment of neurodegenerative disorders. Data reviewed document that a host of products from plant species and derivatives have neuroprotectant effects in vitro and in vivo. In addition, besides neuroprotection, natural products also demonstrate biological effects that target biochemical pathways underlying associated symptoms of neurdegnerative disorders that include cognitive impairments, energy/fatigue, mood, and anxiety. This part of the review series focuses specifically upon Alzheimer's Disease (AD). AD is... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=4016066 Tue, 28 Sep 2010 23:00:00 +0100 4016066 http://www.medworm.com/index.php?rid=4016065&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%3D20874702%26dopt%3DAbstract Authors: Campos HC, da Rocha MD, Viegas FP, Nicastro PC, Fossaluzza PC, Fraga CA, Barreiro EJ, Viegas C Neurodegenerative disorders such as Parkinson's disease (PD), Alzheimer's disease (AD), Huntington's disease (HD) and amyotrophic lateral sclerosis (ALS) are currently incurable pathologies with huge social and economic impacts closely related to the increasing of life expectancy in modern times. Although the clinical and neuropathological aspects of these debilitating disorders are distinct, they share a pattern of neurodegeneration in anatomically or functionally related regions. For each disease, presently available treatments only address symptoms and do not alter the course or progression of the underlying diseases. In this context, the search for new effective chemical entities... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=4016065 Tue, 28 Sep 2010 23:00:00 +0100 4016065 http://www.medworm.com/index.php?rid=4016064&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%3D20874703%26dopt%3DAbstract Authors: De Berardis D, Di Iorio G, Acciavatti T, Conti C, Serroni N, Olivieri L, Cavuto M, Martinotti G, Janiri L, Saverio F, Pio Conti M, Di Giannantonio M Major Depressive Disorder (MDD) is an extremely disabling, chronic and recurrent disease. Moreover, subthreshold depressive symptoms often persist during periods of apparent remission. Such symptoms include sleep disturbances, sexual dysfunction, weight gain, fatigue, disinterest, anxiety, and/or emotional blunting, which do not often respond to available antidepressant treatments. Agomelatine is a melatonergic agonist (at both MT1 and MT2 receptors) and serotonin 2C (5-HT2C) receptor antagonist. Agomelatine should be particularly useful in the treatment of MDD because of its unique pharmacological profile, accounting for its effe... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=4016064 Tue, 28 Sep 2010 23:00:00 +0100 4016064 http://www.medworm.com/index.php?rid=4016063&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%3D20874704%26dopt%3DAbstract Authors: Lehmann HC, Höke A Schwann cells, the myelin forming cells in the peripheral nervous system, play a key role in the pathology of various inflammatory, metabolic and hereditary polyneuropathies. Advances in identifying growth factors and signaling molecules that are expressed by Schwann cells have paved the way to development of new treatment strategies that are aimed to improve the protective and regenerative properties of Schwann cells in peripheral nerve disorders. These include the exogenous application of growth factors and neurohormones which have been advanced into clinical trials in humans, and transplantation paradigms that have been moved into late stage preclinical models. In this review we will discuss the latest developments in these therapeutic approaches with ... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=4016063 Tue, 28 Sep 2010 23:00:00 +0100 4016063 http://www.medworm.com/index.php?rid=3762173&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%3D20632962%26dopt%3DAbstract Authors: White CM, Ji S, Cai H, Maudsley S, Martin B Vasoactive intestinal peptide (VIP) is a basic 28 amino acid peptide that is a member of the class II family of G protein-coupled receptors (GPCRs). It is widely expressed throughout the body and plays an important role in numerous biological functions. VIP acts via three different GPCRs: VPAC1, VPAC2, and PAC1, which have been identified in various tissues, including brain, lung, kidney, gastrointestinal tract, tongue, and also on immunocompetent cells such as macrophages and lymphocytes. There is mounting evidence that VIP expression and signaling is altered in numerous neurological disorders, and it is becoming apparent that VIP and its receptors could be therapeutic loci for the treatment of several pathological conditions of the... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=3762173 Thu, 15 Jul 2010 23:00:00 +0100 3762173 http://www.medworm.com/index.php?rid=3762172&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%3D20632963%26dopt%3DAbstract Authors: Wang L, Chadwick W, Park SS, Zhou Y, Silver N, Martin B, Maudsley S Receptors for hormones of the hypothalamic-pituitary-gonadal axis are expressed throughout the brain. Age-related decline in gonadal reproductive hormones cause imbalances of this axis and many hormones in this axis have been functionally linked to neurodegenerative pathophysiology. Gonadotropin-releasing hormone (GnRH) plays a vital role in both central and peripheral reproductive regulation. GnRH has historically been known as a pituitary hormone; however, in the past few years, interest has been raised in GnRH actions at non-pituitary peripheral targets. GnRH ligands and receptors are found throughout the brain where they may act to control multiple higher functions such as learning and memory function and ... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=3762172 Thu, 15 Jul 2010 23:00:00 +0100 3762172 http://www.medworm.com/index.php?rid=3762170&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%3D20632964%26dopt%3DAbstract Authors: Albizu L, Moreno JL, González-Maeso J, Sealfon SC Because G protein-coupled receptors (GPCRs) are numerous, widely expressed and involved in major physiological responses, they represent a relevant therapeutic target for drug discovery, particularly regarding pharmacological treatments of neurological disorders. Among the biological phenomena regulating receptor function, GPCR heteromerization is an important emerging area of interest and investigation. There is increasing evidence showing that heteromerization contributes to the pharmacological heterogeneity of GPCRs by modulating receptor ontogeny, activation and recycling. Although in many cases the physiological relevance of receptor heteromerization has not been fully established, the unique pharmacological and functio... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=3762170 Thu, 15 Jul 2010 23:00:00 +0100 3762170 http://www.medworm.com/index.php?rid=3762168&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%3D20632965%26dopt%3DAbstract Authors: Pantaleo N, Chadwick W, Park SS, Wang L, Zhou Y, Martin B, Maudsley S Our understanding of the complex signaling neurophysiology of the central nervous system has facilitated the exploration of potential novel receptor-ligand system targets for disorders of this most complex organ. In recent years, many relatively neglected receptor-ligand systems have been re-evaluated with respect to their ability to potently modulate discrete tracts in the central nervous system. One such system is the tachykinin (previously neurokinin) system. The multiple heptahelical G protein-coupled receptors and neuropeptide ligands that comprise this system may be significantly involved in more central nervous systems actions than previously thought, including sleep disorders, amyotrophic lateral scl... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=3762168 Thu, 15 Jul 2010 23:00:00 +0100 3762168 http://www.medworm.com/index.php?rid=3762166&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%3D20632966%26dopt%3DAbstract Authors: Lopez-Gimenez JF, Milligan G Internalisation of the mu opioid receptor from the surface of cells is generally achieved by receptor occupancy with agonist ligands of high efficacy. However, in many situations the potent analgesic morphine fails to promote internalisation effectively and whether there is a direct link between this and the propensity for the sustained use of morphine to result in both tolerance and dependence has been studied intensely. Although frequently described as a partial agonist, this characteristic appears insufficient to explain the poor capacity of morphine to promote internalisation of the mu opioid receptor. Experiments performed using both transfected cell systems and ex vivo/in vivo models have provided evidence that when morphine can promote inter... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=3762166 Thu, 15 Jul 2010 23:00:00 +0100 3762166 http://www.medworm.com/index.php?rid=3762164&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%3D20632967%26dopt%3DAbstract Authors: de Maturana RL, Sánchez-Pernaute R Dopamine modulation of excitatory neurotransmission is critical in the control of movement, emotion and reward. In the striatum, medium size spiny neurons (MSNs) are responsible for the integration of cortical and thalamic information that flows through parallel, partly overlapping, loops and determines adequate experience-dependent responses. Dopamine acts on MSNs through two sets of G protein-coupled receptors (GPCRs), the D1-like and D2-like receptors, which can have opposing or synergistic downstream effects. Notably, these two types of striatal dopamine receptors are segregated into the striatonigral (direct) and striatopallidal (indirect) projecting neurons. Thus, dopamine receptor expression determines the morphological and function... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=3762164 Thu, 15 Jul 2010 23:00:00 +0100 3762164 http://www.medworm.com/index.php?rid=3762162&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%3D20632968%26dopt%3DAbstract Authors: Ferré S, Lluis C, Lanciego JL, Franco R A number of G-protein-coupled receptors (GPCRs) are currently under consideration as potential therapeutic targets for drugs acting in the central nervous system (CNS). Attempts to discover new medications have operated under the assumption that GPCRs are monomers and that a specific drug activates one single receptor coupled to one single signal transduction mechanism. In the neuronal membrane, GPCRs are now known to be arranged into homo- and hetero-oligomers; drugs acting on a single receptor within a specific heteromer context are thought to induce a particular downstream signaling. However, there is recent evidence showing that heteromer-tailored drugs can be designed that display different affinities for a given receptor dependi... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=3762162 Thu, 15 Jul 2010 23:00:00 +0100 3762162 http://www.medworm.com/index.php?rid=3762160&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%3D20632969%26dopt%3DAbstract Authors: Ribeiro FM, Paquet M, Cregan SP, Ferguson SS Stimulation of Group I metabotropic glutamate receptors (mGluR1 and mGluR5) leads to activation of a wide variety of signalling pathways. mGluRs couple to Galpha(q/11) proteins, activating phospholipase Cbeta1 resulting in both diacylglycerol and inositol-1,4,5-triphosphate formation followed by the activation of protein kinase C. In addition, mGluR activation can lead to modulation of a number of ion channels, such as different types of calcium and potassium channels. Group I mGluRs can also activate other downstream protein kinases, such as ERK1/2 and AKT, which are implicated in cellular growth, differentiation, and survival. Moreover, Group I mGluRs interact with a variety of different proteins that are important for the regulat... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=3762160 Thu, 15 Jul 2010 23:00:00 +0100 3762160 http://www.medworm.com/index.php?rid=3762156&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%3D20632970%26dopt%3DAbstract Authors: Bisogno T, Di Marzo V The G-protein coupled receptors for Delta(9)-tetrahydrocannabinol, the major psychoactive principle of marijuana, are known as cannabinoid receptors of type 1 (CB(1)) and 2 (CB(2)) and play important functions in degenerative and inflammatory disorders of the central nervous system. Whilst CB(1) receptors are mostly expressed in neurons, where they regulate neurotransmitter release and synaptic strength, CB(2) receptors are found mostly in glial cells and microglia, which become activated and over-express these receptors during disorders such as Alzheimer's disease, multiple sclerosis, amyotropic lateral sclerosis, Parkinson's disease, and Huntington's chorea. The neuromodulatory actions at CB(1) receptors by endogenous agonists ('endocannabinoids'), of w... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=3762156 Thu, 15 Jul 2010 23:00:00 +0100 3762156 http://www.medworm.com/index.php?rid=3762153&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%3D20632971%26dopt%3DAbstract Authors: Cong WN, Golden E, Pantaleo N, White CM, Maudsley S, Martin B The neuroendocrine hormone ghrelin is an octanoylated 28-residue peptide that exerts numerous physiological functions. Ghrelin exerts its effects on the body mainly through a highly conserved G protein-coupled receptor known as the growth hormone secretagagogue receptor subtype 1a (GHS-R1a). Ghrelin and GSH-R1a are widely expressed in both peripheral and central tissues/organs, and ghrelin signaling plays a critical role in maintaining energy balance and neuronal health. The multiple orexigenic effects of ghrelin and its receptor have been studied in great detail, and GHS-R1a-mediated ghrelin signaling has long been a promising target for the treatment of metabolic disorders, such as obesity. In addition to its well... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=3762153 Thu, 15 Jul 2010 23:00:00 +0100 3762153 http://www.medworm.com/index.php?rid=3762150&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%3D20632972%26dopt%3DAbstract Authors: Bunnett NW, Cottrell GS G protein-coupled receptors (GPCRs) are expressed throughout the nervous system where they regulate multiple physiological processes, participate in neurological diseases, and are major targets for therapy. Given that many GPCRs respond to neurotransmitters and hormones that are present in the extracellular fluid and which do not readily cross the plasma membrane, receptor trafficking to and from the plasma membrane is a critically important determinant of cellular responsiveness. Moreover, trafficking of GPCRs throughout the endosomal system can initiate signaling events that are mechanistically and functionally distinct from those operating at the plasma membrane. This review discusses recent advances in the relationship between signaling and traffick... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=3762150 Thu, 15 Jul 2010 23:00:00 +0100 3762150 http://www.medworm.com/index.php?rid=3762146&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%3D20632973%26dopt%3DAbstract Authors: Cadet JL, Jayanthi S, McCoy MT, Beauvais G, Cai NS Dopamine (DA), the most abundant catecholamine in the basal ganglia, participates in the regulation of motor functions and of cognitive processes such as learning and memory. Abnormalities in dopaminergic systems are thought to be the bases for some neuropsychiatric disorders including addiction, Parkinson's disease, and Schizophrenia. DA exerts its arrays of functions via stimulation of D1-like (D1 and D5) and D2-like (D2, D3, and D4) DA receptors which are located in various regions of the brain. The DA D1 and D2 receptors are very abundant in the basal ganglia where they exert their functions within separate neuronal cell types. The present paper focuses on a review of the effects of stimulation of DA D1 receptors on divers... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=3762146 Thu, 15 Jul 2010 23:00:00 +0100 3762146 http://www.medworm.com/index.php?rid=3762129&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%3D20632974%26dopt%3DAbstract Authors: Maudsley S PMID: 20632974 [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=3762129 Thu, 15 Jul 2010 23:00:00 +0100 3762129 http://www.medworm.com/index.php?rid=3636248&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%3D20522006%26dopt%3DAbstract Authors: Skaper SD PMID: 20522006 [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=3636248 Thu, 03 Jun 2010 23:00:00 +0100 3636248 http://www.medworm.com/index.php?rid=3636247&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%3D20522007%26dopt%3DAbstract Authors: Hirth F Human neurodegenerative diseases are devastating illnesses that predominantly affect elderly people. The majority of the diseases are associated with pathogenic oligomers from misfolded proteins, eventually causing the formation of aggregates and the progressive loss of neurons in the brain and nervous system. Several of these proteinopathies are sporadic and the cause of pathogenesis remains elusive. Heritable forms are associated with genetic defects, suggesting that the affected protein is causally related to disease formation and/or progression. The limitations of human genetics, however, make it necessary to use model systems to analyse affected genes and pathways in more detail. During the last two decades, research using the genetically amenable fruitfly has est... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=3636247 Thu, 03 Jun 2010 23:00:00 +0100 3636247 http://www.medworm.com/index.php?rid=3636246&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%3D20522008%26dopt%3DAbstract Authors: Peviani M, Caron I, Pizzasegola C, Gensano F, Tortarolo M, Bendotti C Amyotrophic Lateral Sclerosis (ALS), which accounts for the majority of motor neuron disorders, is a progressive and fatal neurodegenerative disease leading to complete paralysis of skeletal muscles and premature death usually from respiratory failure. About 10% of all ALS cases are inherited, with the responsible gene having been identified in approximately 25% of these individuals. Mutations in the copper-zinc superoxide dismutase (SOD1) gene were the first to be recognized nearly twenty years ago, and since then different animal models, in particular transgenic rodents, have been developed. They replicate many of the clinical, neuropathological and molecular features of ALS patients and have contributed s... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=3636246 Thu, 03 Jun 2010 23:00:00 +0100 3636246 http://www.medworm.com/index.php?rid=3636245&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%3D20522009%26dopt%3DAbstract This article will describe the above experimental PD models and demonstrate the utility of microdialysis for their characterization. PMID: 20522009 [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=3636245 Thu, 03 Jun 2010 23:00:00 +0100 3636245 http://www.medworm.com/index.php?rid=3636244&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%3D20522010%26dopt%3DAbstract Authors: Cavallarin N, Vicario M, Negro A Synuclein is a soluble, natively unfolded protein that is highly enriched in the presynaptic terminals of neurons in the central nervous system. Interest in -synuclein has increased markedly following the discovery of a relationship between its dysfunction and several neurodegenerative diseases, including Parkinson's disease. The physiological functions of -synuclein remain to be fully defined, although recent data suggest a role in regulating membrane stability and neuronal plasticity. In addition, there is increasing evidence pointing to phosphorylation as playing an important role in the oligomerization, fibrillogenesis, Lewy body formation, and neurotoxicity of -syncline in Parkinson's disease. Immunohistochemical and biochemical studies re... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=3636244 Thu, 03 Jun 2010 23:00:00 +0100 3636244 http://www.medworm.com/index.php?rid=3636243&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%3D20522011%26dopt%3DAbstract This article will provide an overview of the genetics underlying PD and HD, the animal models developed, and their potential utility to the study of disease pathophysiology. PMID: 20522011 [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=3636243 Thu, 03 Jun 2010 23:00:00 +0100 3636243 http://www.medworm.com/index.php?rid=3636242&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%3D20522012%26dopt%3DAbstract Authors: Fernández-Checa JC, Fernández A, Morales A, Marí M, García-Ruiz C, Colell A Oxidative stress has been consistently linked to ageing-related neurodegenerative diseases leading to the generation of lipid peroxides, carbonyl proteins and oxidative DNA damage in tissue samples from affected brains. Studies from mouse models that express disease-specific mutant proteins associated to the major neurodegenerative processes have underscored a critical role of mitochondria in the pathogenesis of these diseases. There is strong evidence that mitochondrial dysfunction is an early event in neurodegeneration. Mitochondria are the main cellular source of reactive oxygen species and key regulators of cell death. Moreover, mitochondria are highly dynamic organelles that divide, fu... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=3636242 Thu, 03 Jun 2010 23:00:00 +0100 3636242 http://www.medworm.com/index.php?rid=3636241&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%3D20522013%26dopt%3DAbstract Authors: Fillat C, Dierssen M, de Lagrán MM, Altafaj X Individuals with trisomy 21, also known as Down syndrome (DS), develop a clinical syndrome including almost identical neuropathological characteristics of Alzheimer's disease (AD) observed in non-DS individuals. The main difference is the early age of onset of AD pathology in individuals with DS, with hish incidence of clinical symptoms in the late 40- early 50 years of age. The neuropathology of AD in persons with DS is superimposed with the developmental abnormalities causing alterations of neuronal morphology and function. Despite the ubiquitous occurrence of AD neuropathology, clinical signs of dementia do not occur in all adults with DS even at older ages. Phenotype analysis of DS mouse models has revealed a differential ag... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=3636241 Thu, 03 Jun 2010 23:00:00 +0100 3636241 http://www.medworm.com/index.php?rid=3636240&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%3D20522014%26dopt%3DAbstract Authors: Noble W, Hanger DP, Gallo JM Tauopathies, including Alzheimer's disease, are neurodegenerative diseases characterized by the deposition of hyperphosphorylated tau protein in the central nervous system, and are the major cause of dementia in later life. Considerable advances have been made in developing mouse models that recapitulate, to varying extents, the development of human tau pathology, and the learning and memory deficits characteristic of some tauopathies. Furthermore, such models have been used to show promising diseasemodifying effects in pre-clinical testing of new therapeutics. Various strategies have been utilised to generate mouse models of tauopathies. Some of the most enlightening models developed to date either constitutively or inducibly express pathogenic ta... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=3636240 Thu, 03 Jun 2010 23:00:00 +0100 3636240 http://www.medworm.com/index.php?rid=3636239&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%3D20522015%26dopt%3DAbstract Authors: Hussain I A critical requirement in the development of Alzheimer's disease (AD) therapeutics is a demonstration of the in vivo efficacy of compounds in pre-clinical disease relevant models. One of the most frequently used models in AD research are transgenic mice overexpressing mutant forms of human amyloid precursor protein (APP) that are associated with early-onset familial AD. These mice exhibit an age-dependent accumulation and deposition of amyloid -peptide (A) as extracellular plaques in the brain, and thereby depict one of the key pathologies observed in the brains of AD patients. Although these mouse models do not recapitulate all the pathological features of AD, they have been invaluable in the development of therapeutic agents aimed at lowering A production, inhibiti... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=3636239 Thu, 03 Jun 2010 23:00:00 +0100 3636239 http://www.medworm.com/index.php?rid=3636238&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%3D20522016%26dopt%3DAbstract Authors: Wilcock DM Alzheimer's disease is a progressive, neurodegenerative disorder characterized by a devastating cognitive decline. The disease is identified pathologically by amyloid plaques composed of aggregated amyloid- peptide, neurofibrillary tangles composed of aggregated, hyperphosphorylated tau protein and neuron loss. While the disease was first described in 1906, transgenic mouse models for the study of Alzheimer's disease pathologies have only been available to scientists for fifteen years. Despite the generation of many different mouse models that develop amyloid plaques or neurofibrillary tangles, it has only been in recent years that mouse models demonstrating the two pathologies together have been made. Also, neuron loss has been difficult to achieve in many models. ... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=3636238 Thu, 03 Jun 2010 23:00:00 +0100 3636238 http://www.medworm.com/index.php?rid=3534508&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%3D20438439%26dopt%3DAbstract Authors: L'episcopo F, Tirolo C, Testa N, Caniglia S, Morale MC, Marchetti B Parkinsons'disease (PD) is a common neurodegenerative disorder characterized by the presence of tremor, muscle rigidity, slowness of voluntary movements and postural instability. One of the pathological hallmarks of PD is loss of dopaminergic (DAergic) neurons in the subtantia nigra pars compacta (SNpc). The cause and mechanisms underlying the demise of nigrostriatal DAergic neurons are not fully understood, but interactions between genes and environmental factors are recognized to play a critical role in modulating the vulnerability to PD. Current evidence points to reactive glia as a pivotal factor in PD, but whether astroglia activation may protect or exacerbate DAergic neuron loss is the subject of much de... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=3534508 Tue, 04 May 2010 23:00:00 +0100 3534508 http://www.medworm.com/index.php?rid=3534507&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%3D20438440%26dopt%3DAbstract Authors: Schmidt AL, Brunetto AL, Schwartsmann G, Roesler R, Abujamra AL Medulloblastoma is the most common malignant brain tumor in children. This malignant tumor of the cerebellum commonly affects children and is believed to arise from the precursor cells of the external granule layer or neuroepithelial cells from the cerebellar ventricular zone of the developing cerebellum. The standard treatment, consisting of surgery, craniospinal radiotherapy and chemotherapy, still provides a poor overall survival for infants and young children. Furthermore, the dose of radiation that can be safely given without causing extensive neurocognitive and endocrinologic sequelae is limited. Therefore, understanding the oncogenic pathways that lead to medulloblastoma, as well as the identification of sp... CNS and Neurological Disorders Drug Targets journals http://www.medworm.com/rss/comments.php?id=3534507 Tue, 04 May 2010 23:00:00 +0100 3534507 http://www.medworm.com/index.php?rid=3487519&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%3D20401980%26dopt%3DAbstract Authors: Rahman S PMID: 20401980 [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=3487519 Wed, 31 Mar 2010 23:00:00 +0100 3487519 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