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 'Molecular Neurodegeneration' source. Sun, 21 Mar 2010 15:31:17 +0100 http://www.medworm.com/index.php?rid=3380852&cid=s_34083_25_f&fid=34083&url=http%3A%2F%2Fwww.molecularneurodegeneration.com%2Fcontent%2F5%2F1%2F11 In this study, the genotype and allele frequencies of the UCHL1 S18Y polymorphism were investigated in 452 AD patients and 234 control subjects, recruited from four memory clinics in Sweden. Using a binary logistic regression model including UCHL1 allele A and APOE epsilon4 allele positivity, age and sex as covariates with AD diagnosis as dependent variable, an adjusted OR of 0.82 ([95% CI 0.55-1.24], P=0.35) was obtained for a positive UCHL1 allele A carrier status. The present study thus do not support a protective effect of the UCHL1 S18Y polymorphism against AD. (Source: Molecular Neurodegeneration) Molecular Neurodegeneration journals http://www.medworm.com/rss/comments.php?id=3380852 Fri, 19 Mar 2010 00:00:00 +0100 3380852 http://www.medworm.com/index.php?rid=3256796&cid=s_34083_25_f&fid=34083&url=http%3A%2F%2Fwww.molecularneurodegeneration.com%2Fcontent%2F5%2F1%2F9 Conclusions: These results support the hypothesis that presynaptic localization involves a mechanism that requires helical conformation and lipid binding. Conversely, the rate of axonal transport is not determined by lipid affinity and is not sufficient to account for differences in presynaptic localization of alpha-synuclein-eGFP variants. (Source: Molecular Neurodegeneration) Molecular Neurodegeneration journals http://www.medworm.com/rss/comments.php?id=3256796 Tue, 09 Feb 2010 00:00:00 +0100 3256796 http://www.medworm.com/index.php?rid=3229353&cid=s_34083_25_f&fid=34083&url=http%3A%2F%2Fwww.molecularneurodegeneration.com%2Fcontent%2F5%2F1%2F8 Conclusions: We conclude that the haplogroup cluster IWX was associated with FTLD in our cohort. Further studies in other ethnically distinct cohorts are needed to clarify the contribution of mtDNA haplogroups to FTLD and AD. (Source: Molecular Neurodegeneration) Molecular Neurodegeneration journals http://www.medworm.com/rss/comments.php?id=3229353 Tue, 02 Feb 2010 00:00:00 +0100 3229353 http://www.medworm.com/index.php?rid=3210267&cid=s_34083_25_f&fid=34083&url=http%3A%2F%2Fwww.molecularneurodegeneration.com%2Fcontent%2F5%2F1%2F7 Conclusions: Since p53 and GSK3beta are both involved in the apoptotic pathway, and GSK3beta overactivity leads to increased levels of plaques and tangles, our model might explain the link between protein aggregation and neuronal loss in neurodegeneration. (Source: Molecular Neurodegeneration) Molecular Neurodegeneration journals http://www.medworm.com/rss/comments.php?id=3210267 Tue, 26 Jan 2010 00:00:00 +0100 3210267 http://www.medworm.com/index.php?rid=3195652&cid=s_34083_25_f&fid=34083&url=http%3A%2F%2Fwww.molecularneurodegeneration.com%2Fcontent%2F5%2F1%2F6 Prion diseases are disorders of protein conformation in which PrPC, the normal cellular conformer, is converted to an abnormal, protease-resistant conformer rPrPSc. Approximately 80% of rPrPSc accumulates in neuronal plasma membranes where it changes their physical properties and profoundly affects membrane functions. In this review we explain how rPrPSc is transported along axons to presynaptic boutons and how we envision the conversion of PrPC to rPrPSc in the postsynaptic membrane. This information is a prerequisite to the second half of this review in which we present evidence that rPrPSc accumulation in synaptic regions links Notch-1 signaling with the dendritic degeneration. The hypothesis that the Notch-1 intracellular domain, NICD, is involved in prion disease was tested by treatin... Molecular Neurodegeneration journals http://www.medworm.com/rss/comments.php?id=3195652 Thu, 21 Jan 2010 00:00:00 +0100 3195652 http://www.medworm.com/index.php?rid=3187299&cid=s_34083_25_f&fid=34083&url=http%3A%2F%2Fwww.molecularneurodegeneration.com%2Fcontent%2F5%2F1%2F5 Conclusions: Our results demonstrate that at 3 weeks, axotomized cholinergic neurons lose their cholinergic phenotype without dying and down-regulate their NGF-receptors, precluding the possibility of a response to NGF. Therefore, the physiological role of NGF in the adult septal cholinergic system is to support phenotypic differentiation and not survival of neurons. This evidence raises questions about the relationship between transcriptional regulation of the cholinergic phenotype by retrograde-derived trophic signaling and the transcriptional changes experienced when retrograde transport is impaired due to neuropathological conditions. (Source: Molecular Neurodegeneration) Molecular Neurodegeneration journals http://www.medworm.com/rss/comments.php?id=3187299 Tue, 19 Jan 2010 00:00:00 +0100 3187299 http://www.medworm.com/index.php?rid=3183751&cid=s_34083_25_f&fid=34083&url=http%3A%2F%2Fwww.molecularneurodegeneration.com%2Fcontent%2F5%2F1%2F3 Conclusion: These results indicate that post-synaptic damage induced by Abeta oligomers in hippocampal neurons is prevented by the non-canonical Wnt pathway activation. (Source: Molecular Neurodegeneration) Molecular Neurodegeneration journals http://www.medworm.com/rss/comments.php?id=3183751 Mon, 18 Jan 2010 00:00:00 +0100 3183751 http://www.medworm.com/index.php?rid=3183750&cid=s_34083_25_f&fid=34083&url=http%3A%2F%2Fwww.molecularneurodegeneration.com%2Fcontent%2F5%2F1%2F4 We report here, that the treatment of rat hippocampal neurons with Abeta-acetylcholinesterase (Abeta-AChE) complexes induced neurite network dystrophia and apoptosis. Moreover, the Abeta-AChE complexes induced a sustained increase in intracellular Ca2+ as well as a loss of mitochondrial membrane potential. The Abeta-AChE oligomers complex also induced higher alteration of Ca2+ homeostasis compared with Abeta-AChE fibrillar complexes. These alterations in calcium homeostasis were reversed when the neurons were treated previously with lithium, a GSK-3beta inhibitor; Wnt-7a ligand, an activator for Wnt Pathway; and an N-methyl-D-aspartate (NMDA) receptor antagonist (MK-801), demonstrating protective roles for activation of the Wnt signaling pathway as well as for NMDA-receptor inhibition. Our... Molecular Neurodegeneration journals http://www.medworm.com/rss/comments.php?id=3183750 Mon, 18 Jan 2010 00:00:00 +0100 3183750 http://www.medworm.com/index.php?rid=3173942&cid=s_34083_25_f&fid=34083&url=http%3A%2F%2Fwww.molecularneurodegeneration.com%2Fcontent%2F5%2F1%2F1 Conclusions: These results implicate NYGGF4 as a novel and specific interactor of LRP1. Decreased expression of LRP1 and NYGGF4 over disease, evident with the presence of even moderate numbers of neuritic plaques, suggests that LRP1-NYGGF4 is a system altered early in disease. Genetic and functional studies have implicated both LRP1 and NYGGF4 in obesity and cardiovascular disease and the physical association of these proteins may reflect a common mechanism. This is particularly interesting in light of the dual role of ApoE in both cardiovascular risk and AD. The results support further studies on the functional relationship between NYGGF4 and LRP1. (Source: Molecular Neurodegeneration) Molecular Neurodegeneration journals http://www.medworm.com/rss/comments.php?id=3173942 Thu, 14 Jan 2010 00:00:00 +0100 3173942 http://www.medworm.com/index.php?rid=3173941&cid=s_34083_25_f&fid=34083&url=http%3A%2F%2Fwww.molecularneurodegeneration.com%2Fcontent%2F5%2F1%2F2 Conclusion: SAD patients and PSEN1 A431E mutation carriers are characterized by aberrant CSF Abeta isoform patterns that hold clinically relevant diagnostic information. PSEN1 A431E mutation carriers exhibit low levels of Abeta1-37, Abeta1-38 and Abeta1-39; fragments that are normally produced by gamma-secretase, suggesting that the PSEN1 A431E mutation modulates gamma-secretase cleavage site preference in a disease-promoting manner. (Source: Molecular Neurodegeneration) Molecular Neurodegeneration journals http://www.medworm.com/rss/comments.php?id=3173941 Thu, 14 Jan 2010 00:00:00 +0100 3173941 http://www.medworm.com/index.php?rid=3131672&cid=s_34083_25_f&fid=34083&url=http%3A%2F%2Fwww.molecularneurodegeneration.com%2Fcontent%2F4%2F1%2F55 Conclusion: The results suggest that chronic low dose rotenone treatment activates human microglia (cell line) in a manner similar to microglia of animal origin as shown by others. However human microglia release excessive amounts of ROS extracellularly, do not show excessive amounts of intracellular ROS and active caspases and most importantly do not show any protein aggregation or inclusion body formation. Human microglia appear to be resistant to rotenone (chronic, low dose) induced damage. (Source: Molecular Neurodegeneration) Molecular Neurodegeneration journals http://www.medworm.com/rss/comments.php?id=3131672 Thu, 31 Dec 2009 00:00:00 +0100 3131672 http://www.medworm.com/index.php?rid=3117091&cid=s_34083_25_f&fid=34083&url=http%3A%2F%2Fwww.molecularneurodegeneration.com%2Fcontent%2F4%2F1%2F53 Conclusions: This first study to quantify ZnT3 mRNA levels in human pm brain tissue from individuals with AD and controls has revealed a significant loss of ZnT3 expression in cortical regions, suggesting that neuronal cells in particular show reduced expression of ZnT3 mRNA in the disease. This suggests that altered neuronal Zn2+ handling may be an early event in AD pathogenesis. (Source: Molecular Neurodegeneration) Molecular Neurodegeneration journals http://www.medworm.com/rss/comments.php?id=3117091 Wed, 23 Dec 2009 00:00:00 +0100 3117091 http://www.medworm.com/index.php?rid=3109500&cid=s_34083_25_f&fid=34083&url=http%3A%2F%2Fwww.molecularneurodegeneration.com%2Fcontent%2F4%2F1%2F52 Conclusions: There results argue that while BDNF plays a role in exercise-induced cell proliferation, other factors must contribute to this phenomenon. We also show that dendritic development was impaired in cKO mice maintained in standard housing conditions, and that EE rescued this phenotype. (Source: Molecular Neurodegeneration) Molecular Neurodegeneration journals http://www.medworm.com/rss/comments.php?id=3109500 Mon, 21 Dec 2009 00:00:00 +0100 3109500 http://www.medworm.com/index.php?rid=3098460&cid=s_34083_25_f&fid=34083&url=http%3A%2F%2Fwww.molecularneurodegeneration.com%2Fcontent%2F4%2F1%2F51 Conclusions: Here, we report the surprising association of acute latrepirdine dosing with elevated levels of extracellular Abeta as measured in three independent neuron-related or neuron-derived systems, including the hippocampus of freely moving Tg2576 mice. Given the reported association of chronic latrepirdine treatment with improvement in cognitive function, the effects of chronic latrepirdine treatment on extracellular Abeta levels must now be determined. (Source: Molecular Neurodegeneration) Molecular Neurodegeneration journals http://www.medworm.com/rss/comments.php?id=3098460 Thu, 17 Dec 2009 00:00:00 +0100 3098460 http://www.medworm.com/index.php?rid=3077489&cid=s_34083_25_f&fid=34083&url=http%3A%2F%2Fwww.molecularneurodegeneration.com%2Fcontent%2F4%2F1%2F49 In this study, we used a rotenone rat midbrain culture model to identify genes that are changed after addition of the neurotoxin. (1) We challenged rat midbrain cultures with rotenone (20nM), a pesticide that has been shown to be toxic for dopaminergic neurons and that has been a well-characterized model of PD. A gene chip array analysis demonstrated that several genes were up-regulated after the rotenone treatment. Interestingly transcriptional activation of vascular endothelial growth factor B (VEGF-B) was evident, while vascular endothelial growth factor A (VEGF-A) levels remained unaltered. The results from the gene chip array experiment were verified with real time PCR and semi-quantitative western analysis using beta-actin as the internal standard. (2) We have also found evidence tha... Molecular Neurodegeneration journals http://www.medworm.com/rss/comments.php?id=3077489 Thu, 10 Dec 2009 00:00:00 +0100 3077489 http://www.medworm.com/index.php?rid=3077488&cid=s_34083_25_f&fid=34083&url=http%3A%2F%2Fwww.molecularneurodegeneration.com%2Fcontent%2F4%2F1%2F50 Conclusions: The results from this study reveal that PEA protects HT22 cells from oxidative stress and alters the localization and expression levels of kinases known to be involved in neuroprotection by a novel mechanism. Overall, these results identify PEA as a neuroprotectant with potential as a possible therapeutic agent in neurodegenerative diseases involving oxidative stress. (Source: Molecular Neurodegeneration) Molecular Neurodegeneration journals http://www.medworm.com/rss/comments.php?id=3077488 Thu, 10 Dec 2009 00:00:00 +0100 3077488 http://www.medworm.com/index.php?rid=3020862&cid=s_34083_25_f&fid=34083&url=http%3A%2F%2Fwww.molecularneurodegeneration.com%2Fcontent%2F4%2F1%2F48 Synapse loss is an early and invariant feature of Alzheimer's disease (AD) and there is a strong correlation between the extent of synapse loss and the severity of dementia. Accordingly, it has been proposed that synapse loss underlies the memory impairment evident in the early phase of AD and that since plasticity is important for neuronal viability, persistent disruption of plasticity may account for the frank cell loss typical of later phases of the disease. Extensive multi-disciplinary research has implicated the amyloid-beta protein (Abeta) in the aetiology of AD and here we review the evidence that non-fibillar soluble forms of Abeta are mediators of synaptic compromise. We also discuss the possible mechanisms of Abeta synaptotoxicity and potential targets for therapeutic interventio... Molecular Neurodegeneration journals http://www.medworm.com/rss/comments.php?id=3020862 Mon, 23 Nov 2009 00:00:00 +0100 3020862 http://www.medworm.com/index.php?rid=2997619&cid=s_34083_25_f&fid=34083&url=http%3A%2F%2Fwww.molecularneurodegeneration.com%2Fcontent%2F4%2F1%2F47 While peripheral immune access to the central nervous system (CNS) is restricted and tightly controlled, the CNS is capable of dynamic immune and inflammatory responses to a variety of insults. Infections, trauma, stroke, toxins and other stimuli are capable of producing an immediate and short lived activation of the innate immune system within the CNS. This acute neuroinflammatory response includes activation of the resident immune cells (microglia) resulting in a phagocytic phenotype and the release of inflammatory mediators such as cytokines and chemokines. While an acute insult may trigger oxidative and nitrosative stress, it is typically short-lived and unlikely to be detrimental to long-term neuronal survival. In contrast, chronic neuroinflammation is a long-standing and often self-p... Molecular Neurodegeneration journals http://www.medworm.com/rss/comments.php?id=2997619 Mon, 16 Nov 2009 00:00:00 +0100 2997619 http://www.medworm.com/index.php?rid=2961285&cid=s_34083_25_f&fid=34083&url=http%3A%2F%2Fwww.molecularneurodegeneration.com%2Fcontent%2F4%2F1%2F46 Conclusions: These results confirm that FL-SORL1 expression declines in AD and with AD-associated neuropathology, suggest that FL-SORL1 declines in cognitively-intact individuals with AD-associated neuropathology, identify a novel SORL1 splice variant that is expressed similarly in AD and non-AD individuals, and provide evidence that an AD-associated SNP is associated with SORL1 expression. Overall, these results contribute to our understanding of SORL1 expression in the human brain. (Source: Molecular Neurodegeneration) Molecular Neurodegeneration journals http://www.medworm.com/rss/comments.php?id=2961285 Wed, 04 Nov 2009 00:00:00 +0100 2961285 http://www.medworm.com/index.php?rid=2932839&cid=s_34083_25_f&fid=34083&url=http%3A%2F%2Fwww.molecularneurodegeneration.com%2Fcontent%2F4%2F1%2F44 In this study, we found that neurons showed an increase in viability after treatment with either L-type or T-type calcium channel antagonists. The family of low-voltage activated, or T-type calcium channels, comprise of three members (Cav3.1, Cav3.2, and Cav3.3) based on their respective main pore-forming alpha subunits: alpha 1G, alpha 1H, and alpha 1I. Among these three subunits, alpha 1H is highly expressed in hippocampus and certain cortical regions. However, T-type calcium channel blockers can protect neurons derived from alpha 1H-/- mice, suggesting that neuroprotection demonstrated by these drugs is not through the alpha 1H subunit. In addition, blockers for T-type calcium channels were not able to confer any protection to neurons in long-term cultures, while blockers of L-type calc... Molecular Neurodegeneration journals http://www.medworm.com/rss/comments.php?id=2932839 Wed, 28 Oct 2009 00:00:00 +0100 2932839 http://www.medworm.com/index.php?rid=2932840&cid=s_34083_25_f&fid=34083&url=http%3A%2F%2Fwww.molecularneurodegeneration.com%2Fcontent%2F4%2F1%2F43 The objectives of this meeting were to (1) promote cutting-edge neurodegeneration research in China and in neighboring Asian countries; (2) facilitate the exchange of information relevant to neurodegenerative research; (3) provide education opportunity for students, postdocs and physicians; and (4) provide a platform for investigators at different career levels to interact and network, and to foster collaborations at the international levels. About 100 investigators presented their recent discoveries with a wide range of scopes of neurodegeneration research, including new genes, molecular pathways, animal models, and potential therapeutics. (Source: Molecular Neurodegeneration) Molecular Neurodegeneration journals http://www.medworm.com/rss/comments.php?id=2932840 Tue, 27 Oct 2009 00:00:00 +0100 2932840 http://www.medworm.com/index.php?rid=2918184&cid=s_34083_25_f&fid=34083&url=http%3A%2F%2Fwww.molecularneurodegeneration.com%2Fcontent%2F4%2F1%2F41 Conclusions: Taken together, we propose that CD74 inhibits Abeta production by interacting with and derailing normal trafficking of APP. (Source: Molecular Neurodegeneration) Molecular Neurodegeneration journals http://www.medworm.com/rss/comments.php?id=2918184 Wed, 21 Oct 2009 23:00:00 +0100 2918184 http://www.medworm.com/index.php?rid=2910479&cid=s_34083_25_f&fid=34083&url=http%3A%2F%2Fwww.molecularneurodegeneration.com%2Fcontent%2F4%2F1%2F40 ObjectiveAlzheimer's disease (AD) is a progressive neurodegenerative disease of the central nervous system (CNS). Recently, an increased interest in the role diet plays in the pathology of AD has resulted in a focus on the detrimental effects of diets high in cholesterol and fat and the beneficial effects of caloric restriction. The current study examines how dietary composition modulates cerebral amyloidosis and neuronal integrity in the TgCRND8 mouse model of AD. Methods: From 4 wks until 18 wks of age, male and female TgCRND8 mice were maintained on one of four diets: (1) reference (regular) commercial chow; (2) high fat/low carbohydrate custom chow (60 kcal% fat/ 30 kcal% protein/ 10 kcal% carbohydrate); (3) high protein/low carbohydrate custom chow (60 kcal% protein/ 30 kcal% fat/ 10 ... Molecular Neurodegeneration journals http://www.medworm.com/rss/comments.php?id=2910479 Tue, 20 Oct 2009 23:00:00 +0100 2910479 http://www.medworm.com/index.php?rid=2896726&cid=s_34083_25_f&fid=34083&url=http%3A%2F%2Fwww.molecularneurodegeneration.com%2Fcontent%2F4%2F1%2F39 Conclusion: We succeeded in developing novel mAbs that selectively detect rodent and/or human IDE, which we have shown to be suitable for a wide range of applications, including western blotting, immunoprecipitation, immunocytochemistry, immunohistochemistry, and quantitative sandwich ELISAs. These novel anti-IDE mAbs and the assays derived from them constitute important new tools for addressing many unresolved questions about the basic biology of IDE and its role in multiple highly prevalent human diseases. (Source: Molecular Neurodegeneration) Molecular Neurodegeneration journals http://www.medworm.com/rss/comments.php?id=2896726 Thu, 15 Oct 2009 23:00:00 +0100 2896726 http://www.medworm.com/index.php?rid=2822392&cid=s_34083_25_f&fid=34083&url=http%3A%2F%2Fwww.molecularneurodegeneration.com%2Fcontent%2F4%2F1%2F37 Conclusions: sPD brain mitochondria have reduced mitochondrial respiratory protein levels in complexes I-V, implying a generalized defect in respirasome assembly. These deficiencies do not appear to arise from altered point mutational burden in mtDNA or reduction of nuclear signaling for mitochondrial biogenesis, implying downstream etiologies. The origin of age-related increases in distribution of oxidative mtDNA damage in sPD but not CTL brains is not clear, tracks with but does not determine the sPD phenotype, and may indicate a unique consequence of aging present in sPD that could contribute to mtDNA deletion generation in addition to mtDNA replication, transcription and sequencing errors. sPD frontal cortex experiences a generalized bioenergetic deficiency above and beyond aging that ... Molecular Neurodegeneration journals http://www.medworm.com/rss/comments.php?id=2822392 Tue, 22 Sep 2009 23:00:00 +0100 2822392 http://www.medworm.com/index.php?rid=2735992&cid=s_34083_25_f&fid=34083&url=http%3A%2F%2Fwww.molecularneurodegeneration.com%2Fcontent%2F4%2F1%2F36 The aim of our study was to analyze the differential expression of miRNAs in the brains of BSE-infected cynomolgus macaques as a model for Creutzfeldt-Jakob disease (CJD). MicroRNAs (miRNAs) are small noncoding RNAs regulating gene expression by mRNA targeting. Among other functions they contribute to neuronal development and survival. Recently, the lack of miRNA processing has been shown to promote neurodegeneration and deregulation of several miRNAs has been reported to be associated with Scrapie in mice. Therefore, we hypothesized that miRNAs are also regulated in response to human prion disease. We have applied miRNA-microarrays to identify deregulated miRNA candidates in brains of BSE-infected macaques. Shock-frozen brain sections of six BSE-infected and five non-infected macaques wer... Molecular Neurodegeneration journals http://www.medworm.com/rss/comments.php?id=2735992 Wed, 26 Aug 2009 23:00:00 +0100 2735992 http://www.medworm.com/index.php?rid=2718050&cid=s_34083_25_f&fid=34083&url=http%3A%2F%2Fwww.molecularneurodegeneration.com%2Fcontent%2F4%2F1%2F35 Conclusions: ApoE4(1-272) fragment expressed in Neuro2a cells is associated with mitochondrial proteins, UQCRC2 and cytochrome C1, which are component of respiratory complex III, and with COX IV 1, which is a member of complex IV. Overexpression of apoE4(1-272) fragment impairs activities of complex III and IV. These results suggest that the C-terminal-truncated fragment of apoE4 binds to mitochondrial complexes and affects their activities, and thereby leading to neurodegeneration. (Source: Molecular Neurodegeneration) Molecular Neurodegeneration journals http://www.medworm.com/rss/comments.php?id=2718050 Wed, 19 Aug 2009 23:00:00 +0100 2718050 http://www.medworm.com/index.php?rid=2636036&cid=s_34083_25_f&fid=34083&url=http%3A%2F%2Fwww.molecularneurodegeneration.com%2Fcontent%2F4%2F1%2F34 Conclusions: We have developed and evaluated novel conditional alpha-synuclein transgenic mice with transgene expression directed selectively to nigrostriatal dopaminergic neurons as a potential new mouse model of PD. Our data support the pathophysiological relevance of C-terminally truncated alpha-synuclein species in vivo. The expression of alpha-Syn119 in the mouse nigrostriatal dopaminergic pathway may provide a useful model of striatal dopamine depletion and could potentially provide a presymptomatic model of PD perhaps representative of the earliest derangements in dopaminergic neuronal function observed prior to neuronal loss. These conditional alpha-synuclein transgenic mice provide novel tools for evaluating and dissecting the age-related effects of alpha-synuclein pathological va... Molecular Neurodegeneration journals http://www.medworm.com/rss/comments.php?id=2636036 Thu, 23 Jul 2009 23:00:00 +0100 2636036 http://www.medworm.com/index.php?rid=2632358&cid=s_34083_25_f&fid=34083&url=http%3A%2F%2Fwww.molecularneurodegeneration.com%2Fcontent%2F4%2F1%2F32 In this study, we demonstrate increased FOXO3 in association with Lewy bodies and Lewy neurites in LBD and PD brain tissue. Since FOXO proteins are involved in several pathways responsible for the regulation of cell death, cell proliferation, and cell metabolism, the ectopic localization of FOXO3 to Lewy bodies provides evidence that aberrations in basic cellular biochemistry may contribute to inclusion formation, which is likely more complex than a simple "gain of function" toxicity as is commonly opined. In light of the known interaction of FOXO3 and 14-3-3, basic protein-protein interaction between these proteins and alpha-synuclein may be key. (Source: Molecular Neurodegeneration) Molecular Neurodegeneration journals http://www.medworm.com/rss/comments.php?id=2632358 Wed, 22 Jul 2009 23:00:00 +0100 2632358 http://www.medworm.com/index.php?rid=2632357&cid=s_34083_25_f&fid=34083&url=http%3A%2F%2Fwww.molecularneurodegeneration.com%2Fcontent%2F4%2F1%2F33 Conclusion: These data suggest that acyl peptide hydrolase is involved in the degradation of oligomeric amyloid-beta, an activity that, if induced, might present a new tool for therapy aimed at reducing neurodegeneration in the Alzheimer's brain. (Source: Molecular Neurodegeneration) Molecular Neurodegeneration journals http://www.medworm.com/rss/comments.php?id=2632357 Wed, 22 Jul 2009 23:00:00 +0100 2632357 http://www.medworm.com/index.php?rid=2618317&cid=s_34083_25_f&fid=34083&url=http%3A%2F%2Fwww.molecularneurodegeneration.com%2Fcontent%2F4%2F1%2F31 Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease of unknown cause, characterized by the selective and progressive death of both upper and lower motoneurons, leading to a progressive paralysis. Experimental animal models of the disease may provide knowledge of the pathophysiological mechanisms and allow the design and testing of therapeutic strategies, provided that they mimic as close as possible the symptoms and temporal progression of the human disease. The principal hypotheses proposed to explain the mechanisms of motoneuron degeneration have been studied mostly in models in vitro, such as primary cultures of fetal motoneurons, organotypic cultures of spinal cord sections from postnatal rodents and the motoneuron-like hybridoma cell line NSC-34. However, these mo... Molecular Neurodegeneration journals http://www.medworm.com/rss/comments.php?id=2618317 Sun, 19 Jul 2009 23:00:00 +0100 2618317 http://www.medworm.com/index.php?rid=2659331&cid=s_34083_25_f&fid=34083&url=http%3A%2F%2Fwww.molecularneurodegeneration.com Correction to Nural H, He P, Beach T, Sue L, Xia W, Shen Y. Dissembled DJ-1 high molecular weight complex in cortex mitochondria from Parkinson's disease patients Molecular Neurodegeneration 2009, 4:23. (Source: Molecular Neurodegeneration) Molecular Neurodegeneration journals http://www.medworm.com/rss/comments.php?id=2659331 Tue, 14 Jul 2009 23:00:00 +0100 2659331 http://www.medworm.com/index.php?rid=2604136&cid=s_34083_25_f&fid=34083&url=http%3A%2F%2Fwww.molecularneurodegeneration.com%2Fcontent%2F4%2F1%2F30 Correction to Nural H, He P, Beach T, Sue L, Xia W, Shen Y. Dissembled DJ-1 high molecular weight complex in cortex mitochondria from Parkinson's disease patients Molecular Neurodegeneration 2009, 4:23. (Source: Molecular Neurodegeneration) Molecular Neurodegeneration journals http://www.medworm.com/rss/comments.php?id=2604136 Tue, 14 Jul 2009 23:00:00 +0100 2604136 http://www.medworm.com/index.php?rid=2599903&cid=s_34083_25_f&fid=34083&url=http%3A%2F%2Fwww.molecularneurodegeneration.com%2Fcontent%2F4%2F1%2F29 Recent studies of inherited neurodegenerative disorders have suggested a linkage between the propensity toward aggregation of mutant protein and disease onset. This is particularly apparent for polyglutamine (polyQ) diseases caused by expansion of CAG-trinucleotide repeats. However, a quantitative framework for relating aggregation kinetics with molecular mechanisms of neurodegeneration initiation is lacking. Here, using the repeat-length-dependent age-of-onset in polyQ diseases, we derived a mathematical model based on nucleation of aggregation kinetics to describe genotype-phenotype correlations, and validated the model using both in vitro data and clinical data. Instead of describing polyQ aggregation kinetics with a derivative equation, our model divided age-of-onset (equivalent to the... Molecular Neurodegeneration journals http://www.medworm.com/rss/comments.php?id=2599903 Tue, 14 Jul 2009 23:00:00 +0100 2599903 http://www.medworm.com/index.php?rid=2599904&cid=s_34083_25_f&fid=34083&url=http%3A%2F%2Fwww.molecularneurodegeneration.com%2Fcontent%2F4%2F1%2F28 Conclusions: Our data indicates that APP can regulate diverse cellular processes and that, vice versa, a network of signaling events can impact APP processing. Our results also suggest that phosphorylation of the APP Intracellular Domain will dramatically shape the APP interactome and, consequently, will regulate APP processing, APP transport and APP/AID-mediated functions. (Source: Molecular Neurodegeneration) Molecular Neurodegeneration journals http://www.medworm.com/rss/comments.php?id=2599904 Mon, 13 Jul 2009 23:00:00 +0100 2599904 http://www.medworm.com/index.php?rid=2525143&cid=s_34083_25_f&fid=34083&url=http%3A%2F%2Fwww.molecularneurodegeneration.com%2Fcontent%2F4%2F1%2F27 Extensive genetic, biochemical, and histological evidence has implicated the amyloid-beta peptide (Abeta) in Alzheimer's disease pathogenesis, and several mechanisms have been suggested, such as metal binding, reactive oxygen species production, and membrane pore formation. However, recent evidence argues for an additional role for signaling mediated by the amyloid precursor protein, APP, in part via the caspase cleavage of APP at aspartate 664. Here we review the effects and implications of this cleavage event, and propose a model of Alzheimer's disease that focuses on the critical nature of this cleavage and its downstream effects. (Source: Molecular Neurodegeneration) Molecular Neurodegeneration journals http://www.medworm.com/rss/comments.php?id=2525143 Thu, 25 Jun 2009 23:00:00 +0100 2525143 http://www.medworm.com/index.php?rid=2492068&cid=s_34083_25_f&fid=34083&url=http%3A%2F%2Fwww.molecularneurodegeneration.com%2Fcontent%2F4%2F1%2F26 Background: It has been hypothesized that reduced axonal transport contributes to the degeneration of neuronal processes in Parkinson's disease (PD). Mitochondria supply the adenosine triphosphate (ATP) needed to support axonal transport and contribute to many other cellular functions essential for the survival of neuronal cells. Furthermore, mitochondria in PD tissues are metabolically and functionally compromised. To address this hypothesis, we measured the velocity of mitochondrial movement in human transmitochondrial cybrid "cytoplasmic hybrid" neuronal cells bearing mitochondrial DNA from patients with sporadic PD and disease-free age-matched volunteer controls (CNT). The absorption of low level, near-infrared laser light by components of the mitochondrial electron transport chain (mt... Molecular Neurodegeneration journals http://www.medworm.com/rss/comments.php?id=2492068 Tue, 16 Jun 2009 23:00:00 +0100 2492068 http://www.medworm.com/index.php?rid=2480467&cid=s_34083_25_f&fid=34083&url=http%3A%2F%2Fwww.molecularneurodegeneration.com%2Fcontent%2F4%2F1%2F25 In conclusion, a reduction of LRRK2 expression in hmNPCs severely impaired dopaminergic differentiation and/or survival of dopaminergic neurons most likely via preserving or reactivating the cell cycle. (Source: Molecular Neurodegeneration) Molecular Neurodegeneration journals http://www.medworm.com/rss/comments.php?id=2480467 Mon, 15 Jun 2009 04:00:00 +0100 2480467 http://www.medworm.com/index.php?rid=2460762&cid=s_34083_25_f&fid=34083&url=http%3A%2F%2Fwww.molecularneurodegeneration.com%2Fcontent%2F4%2F1%2F24 While numerous hypotheses have been proposed to explain the molecular mechanisms underlying the pathogenesis of neurodegenerative diseases, the theory of oxidative stress has received considerable support. Although many correlations have been established and encouraging evidence has been obtained, conclusive proof of causation for the oxidative stress hypothesis is lacking and potential cures have not emerged. Therefore it is likely that other factors, possibly in coordination with oxidative stress, contribute to neuron death. Using Parkinson's disease (PD) as the paradigm, this review explores the hypothesis that oxidative modifications, mitochondrial functional disruption, and impairment of protein degradation constitute three interrelated molecular pathways that execute neuron death. Th... Molecular Neurodegeneration journals http://www.medworm.com/rss/comments.php?id=2460762 Fri, 05 Jun 2009 04:00:00 +0100 2460762 http://www.medworm.com/index.php?rid=2460763&cid=s_34083_25_f&fid=34083&url=http%3A%2F%2Fwww.molecularneurodegeneration.com%2Fcontent%2F4%2F1%2F23 The PARK7 gene encodes a protein, DJ-1, with several functions for the protection of cells from oxidative stress, sperm maturation and fertilization, and chaperone activity. Mutations in the PARK7 gene are associated with autosomal recessive early-onset Parkinson's disease (PD). DJ-1 has been reported to be expressed in multiple cells in the central nervous system. By using both native and denatured Western blots, we examined the levels of total DJ-1 and High molecular weight complexes of DJ-1 (HMW) compared in both the substantia nigra and cortex from rapidly autopsied 18 PD and 9 non-pathological control (NPC) brains. We discovered that, in the PD cortex mitochondria fraction the HMW DJ-1 complex is significantly lower than in the NPC (p (Source: Molecular Neurodegeneration) Molecular Neurodegeneration journals http://www.medworm.com/rss/comments.php?id=2460763 Thu, 04 Jun 2009 04:00:00 +0100 2460763 http://www.medworm.com/index.php?rid=2450358&cid=s_34083_25_f&fid=34083&url=http%3A%2F%2Fwww.molecularneurodegeneration.com%2Fcontent%2F4%2F1%2F22 gamma-Secretase is an aspartyl protease that cleaves multiple substrates that are involved in broad biological processes ranging from stem cell development to neurodegeneration. The investigation of gamma-secretase has been limited by currently available assays that require genetic or biochemical manipulation in the form of substrate transfection or membrane preparation. Here we report an exo-cell assay that is capable of characterizing gamma-secretase activity in any cellular system without limitation. Using a highly active, recombinant substrate this assay can quickly and easily ascertain the status of gamma-secretase activity in cell systems and patient samples. We have applied this method to determine the activity of gamma-secretase in primary cell samples where transfection and/or mem... Molecular Neurodegeneration journals http://www.medworm.com/rss/comments.php?id=2450358 Tue, 02 Jun 2009 04:00:00 +0100 2450358 http://www.medworm.com/index.php?rid=2393581&cid=s_34083_25_f&fid=34083&url=http%3A%2F%2Fwww.molecularneurodegeneration.com%2Fcontent%2F4%2F1%2F19 The gamma-secretase complex is a major therapeutic target for the prevention and treatment of Alzheimer's disease. Previous studies have shown that treatment of young APP mice with specific inhibitors of gamma-secretase prevented formation of new plaques. It has not yet been shown directly whether existing plaques would be affected by gamma-secretase inhibitor treatment. Similarly, alterations in neuronal morphology in the immediate vicinity of plaques represent a plaque-specific neurotoxic effect. Reversal of these alterations is an important endpoint of successful therapy whether or not a treatment affects plaque size. In the present study we used longitudinal imaging in vivo with multiphoton microscopy to study the effects of the orally active gamma-secretase inhibitor LY-411575 in 10-... Molecular Neurodegeneration journals http://www.medworm.com/rss/comments.php?id=2393581 Wed, 06 May 2009 04:00:00 +0100 2393581 http://www.medworm.com/index.php?rid=2393580&cid=s_34083_25_f&fid=34083&url=http%3A%2F%2Fwww.molecularneurodegeneration.com%2Fcontent%2F4%2F1%2F20 Calcium is a key signaling ion involved in many different intracellular and extracellular processes ranging from synaptic activity to cell-cell communication and adhesion. The exact definition at the molecular level of the versatility of this ion has made overwhelming progress in the past several years and has been extensively reviewed. In the brain, calcium is fundamental in the control of synaptic activity and memory formation, a process that leads to the activation of specific calcium-dependent signal transduction pathways and implicates key protein effectors, such as CaMKs, MAPK/ERKs, and CREB. Properly controlled homeostasis of calcium signaling not only supports normal brain physiology but also maintains neuronal integrity and long-term cell survival. Emerging knowledge indicates tha... Molecular Neurodegeneration journals http://www.medworm.com/rss/comments.php?id=2393580 Wed, 06 May 2009 04:00:00 +0100 2393580 http://www.medworm.com/index.php?rid=2335133&cid=s_34083_25_f&fid=34083&url=http%3A%2F%2Fwww.molecularneurodegeneration.com%2Fcontent%2F4%2F1%2F17 Conclusions: Our results demonstrate that LRP1 is shed by ADAM10 and ADAM17 and functional sLRP1 is abundantly present in human brain and CSF. Dysregulated LRP1 shedding during aging could alter its function and may contribute to the pathogenesis of AD. (Source: Molecular Neurodegeneration) Molecular Neurodegeneration journals http://www.medworm.com/rss/comments.php?id=2335133 Thu, 16 Apr 2009 04:00:00 +0100 2335133 http://www.medworm.com/index.php?rid=2311647&cid=s_34083_25_f&fid=34083&url=http%3A%2F%2Fwww.molecularneurodegeneration.com%2Fcontent%2F4%2F1%2F16 Autophagy is the major pathway involved in the degradation of proteins and organelles, cellular remodeling, and survival during nutrient starvation. Autophagosomal dysfunction has been implicated in an increasing number of diseases from cancer to bacterial and viral infections and more recently in neurodegeneration. While a decrease in autophagic activity appears to interfere with protein degradation and possibly organelle turnover, increased autophagy has been shown to facilitate the clearance of aggregation-prone proteins and promote neuronal survival in a number of disease models. On the other hand, too much autophagic activity can be detrimental as well and lead to cell death, suggesting the regulation of autophagy has an important role in cell fate decisions. An increasing number of m... Molecular Neurodegeneration journals http://www.medworm.com/rss/comments.php?id=2311647 Mon, 06 Apr 2009 04:00:00 +0100 2311647 http://www.medworm.com/index.php?rid=2289637&cid=s_34083_25_f&fid=34083&url=http%3A%2F%2Fwww.molecularneurodegeneration.com%2Fcontent%2F4%2F1%2F15 In AtT-20 cells ACTH secretion is regulated by both Ca2+ and G proteins. We previously demonstrated that calnuc, an EF-hand Ca2+ binding protein which regulates Alzheimer's beta-amyloid precursor protein (APP) biogenesis, binds both Ca2+ as well as G alpha subunits. Here we investigate calnuc's role in G protein-mediated regulation of ACTH secretion in AtT-20 neuroendocrine secretory cells stably overexpressing calnuc-GFP. Similar to endogenous calnuc, calnuc-GFP is mainly found in the Golgi, on the plasma membrane (PM), and associated with regulated secretion granules (RSG). By deconvolution immunofluorescence, calnuc-GFP partially colocalizes with G alpha i1/2 and G alpha i3 at the PM and on RSG. Cytosolic calnuc(DSS)-CFP with the signal sequence deleted also partially colocalizes with R... Molecular Neurodegeneration journals http://www.medworm.com/rss/comments.php?id=2289637 Wed, 25 Mar 2009 04:00:00 +0100 2289637 http://www.medworm.com/index.php?rid=2270396&cid=s_34083_25_f&fid=34083&url=http%3A%2F%2Fwww.molecularneurodegeneration.com%2Fcontent%2F4%2F1%2F14 Accumulating evidence suggests that neurons prone to degeneration in Alzheimer's Disease (AD) exhibit evidence of re-entry into an aberrant mitotic cell cycle. Our laboratory recently demonstrated that, in a genomic amyloid precursor protein (APP) mouse model of AD (R1.40), neuronal cell cycle events (CCEs) occur in the absence of beta-amyloid (Abeta) deposition and are still dependent upon the amyloidogenic processing of the amyloid precursor protein (APP). These data suggested that soluble Abeta species might play a direct role in the induction of neuronal CCEs. Here, we show that exposure of non-transgenic mouse primary cortical neurons to Abeta oligomers, but not monomers or fibrils, results in the retraction of neuronal processes, and induction of CCEs in a concentration dependent man... Molecular Neurodegeneration journals http://www.medworm.com/rss/comments.php?id=2270396 Mon, 16 Mar 2009 04:00:00 +0100 2270396 http://www.medworm.com/index.php?rid=2265036&cid=s_34083_25_f&fid=34083&url=http%3A%2F%2Fwww.molecularneurodegeneration.com%2Fcontent%2F4%2F1%2F13 Since the identification of tau as the main component of neurofibrillary tangles in Alzheimer's disease and related tauopathies, and the discovery that mutations in the tau gene cause frontotemporal dementia, much effort has been directed towards determining how the aggregation of tau into fibrillar inclusions causes neuronal death. As evidence emerges that tau-mediated neuronal death can occur even in the absence of tangle formation, a growing number of studies are focusing on understanding how abnormalities in tau (e.g. aberrant phosphorylation, glycosylation or truncation) confer toxicity. Though data obtained from experimental models of tauopathies strongly support the involvement of pathologically modified tau and tau aggregates in neurodegeneration, the exact neurotoxic species remai... Molecular Neurodegeneration journals http://www.medworm.com/rss/comments.php?id=2265036 Wed, 11 Mar 2009 04:00:00 +0100 2265036 http://www.medworm.com/index.php?rid=2222052&cid=s_34083_25_f&fid=34083&url=http%3A%2F%2Fwww.molecularneurodegeneration.com%2Fcontent%2F4%2F1%2F12 Mutations in the DJ-1 gene have been linked to autosomal recessive familial Parkinson's disease. To understand the function of DJ-1, we determined the DJ-1 expression in both zebrafish and post mortem human brains. We found that DJ-1 was expressed early during zebrafish development and throughout adulthood. Knock down (KD) of DJ-1 by injection of morpholino did not cause dramatic morphologic alterations during development, and no loss of dopaminergic neurons was observed in embryos lacking DJ-1. However, DJ-1 KD embryos were more susceptible to programmed cell death. While a slight reduction in staining for islet-1 positive neurons was observed in both DJ-1 KD and H2O2 treated embryos, the number of apoptotic cells was significantly increased in both KD and H2O2 treated embryos. Interesti... Molecular Neurodegeneration journals http://www.medworm.com/rss/comments.php?id=2222052 Wed, 25 Feb 2009 05:00:00 +0100 2222052 http://www.medworm.com/index.php?rid=2172406&cid=s_34083_25_f&fid=34083&url=http%3A%2F%2Fwww.molecularneurodegeneration.com%2Fcontent%2F4%2F1%2F11 Conclusion: We developed neuronal cell lines with inducible expression of wild type and mutant huntingtin. These new cell lines represent a reliable in vitro system for modeling Huntington's disease and should find wide use for high-throughput screening application and for investigating the biology of mutant huntingtin. (Source: Molecular Neurodegeneration) Molecular Neurodegeneration journals http://www.medworm.com/rss/comments.php?id=2172406 Mon, 09 Feb 2009 05:00:00 +0100 2172406 http://www.medworm.com/index.php?rid=2167152&cid=s_34083_25_f&fid=34083&url=http%3A%2F%2Fwww.molecularneurodegeneration.com%2Fcontent%2F4%2F1%2F10 Although there is a strong correlation between CAG repeat length and age at onset (AO) of motor symptoms, individual Huntington disease (HD) patients may differ dramatically in onset age and disease manifestations despite similar CAG repeat lengths. This has led to a search for genetic factors that influence AO. In order to identify such a genetic modifier, we analysed polymorphisms in the PGC-1alpha gene. Recent data indicate inhibition of PGC-1alpha function by mutant Htt supporting a link between transcriptional deregulation and mitochondrial dysfunction in HD. In more than 400 HD patients, a polymorphism located within intron 2, a potential recombination hot spot, explains a small, but statistically significant, amount of the variability in AO. Our data suggest that PGC-1alpha has modi... Molecular Neurodegeneration journals http://www.medworm.com/rss/comments.php?id=2167152 Fri, 06 Feb 2009 05:00:00 +0100 2167152 http://www.medworm.com/index.php?rid=2128551&cid=s_34083_25_f&fid=34083&url=http%3A%2F%2Fwww.molecularneurodegeneration.com%2Fcontent%2F4%2F1%2F3 Huntington's disease (HD) is one of the most common autosomal dominant inherited, neurodegenerative disorders. It is characterized by progressive motor, emotional and cognitive dysfunction. In addition metabolic abnormalities such as wasting and altered energy expenditure are increasingly recognized as clinical hallmarks of the disease. HD is caused by an unstable CAG repeat expansion in the HD gene (HTT), localized on chromosome 4p16.3. The number of CAG repeats in the HD gene is the main predictor of disease-onset, but the remaining variation is strongly heritable. Transcriptional dysregulation, mitochondrial dysfunction and enhanced oxidative stress have been implicated in the pathogenesis. Recent studies suggest that PGC-1α, a transcriptional master regulator of mitochondrial biogenes... Molecular Neurodegeneration journals http://www.medworm.com/rss/comments.php?id=2128551 Thu, 08 Jan 2009 05:00:00 +0100 2128551 http://www.medworm.com/index.php?rid=2089568&cid=s_34083_25_f&fid=34083&url=http%3A%2F%2Fwww.molecularneurodegeneration.com%2Fcontent%2F4%2F1%2F3 Huntington's disease (HD) is one of the most common autosomal dominant inherited neurodegenerative disorders. It is characterized by progressive motor, emotional and cognitive dysfunction. In addition metabolic abnormalities such as wasting and altered energy expenditure are increasingly recognized as clinical hallmarks of the disease. HD is caused by an unstable CAG repeat expansion in the HD gene (HTT), localized on chromosome 4p16.3. The number of CAG repeats in the HD gene is the main predictor of disease-onset, but the remaining variation is strongly heritable. Transcriptional dysregulation, mitochondrial dysfunction and enhanced oxidative stress have been implicated in the pathogenesis. Recent studies suggest that PGC-1alpha, a transcriptional master regulator of mitochondrial biogen... Molecular Neurodegeneration journals http://www.medworm.com/rss/comments.php?id=2089568 Thu, 08 Jan 2009 05:00:00 +0100 2089568 http://www.medworm.com/index.php?rid=2073350&cid=s_34083_25_f&fid=34083&url=http%3A%2F%2Fwww.molecularneurodegeneration.com%2Fcontent%2F3%2F1%2F22 Conclusions: Our results support the notion that optimal substrate degradation by IDE may require its association with organized-DRMs. Alternatively, DRMs but not other plasma membrane regions, may act as platforms where Abeta accumulates, due to its hydrophobic properties, reaching local concentration close to its Km for IDE facilitating its clearance. Structural integrity of DRMs may also be required to tightly retain insulin receptor and IDE for insulin proteolysis. The concept that mis-location of Abeta degrading proteases away from DRMs may impair the physiological turn-over of Abeta in vivo deserves further investigation in light of therapeutic strategies based on enhancing Abeta proteolysis in which DRM protease-targeting may need to be taken into account. (Source: Molecular Neurode... Molecular Neurodegeneration journals http://www.medworm.com/rss/comments.php?id=2073350 Wed, 31 Dec 2008 05:00:00 +0100 2073350 http://www.medworm.com/index.php?rid=2073351&cid=s_34083_25_f&fid=34083&url=http%3A%2F%2Fwww.molecularneurodegeneration.com%2Fcontent%2F3%2F1%2F21 Conclusions: Subacute rotenone treatment of differentiated SH-SY5Y neuroblastoma cells causes process retraction and partial death over several weeks, slowed mitochondrial movement in processes and appears to reproduce the Lewy neuritic changes of early Parkinson's disease pathology but does not cause Lewy body inclusions. The overall pattern of transcriptional regulation is gene under-expression with minimal regulation of ETC genes in spite of rotenone's being a complex I toxin. This rotenone-SH-SY5Y model in a differentiated human neural cell mimics changes of early Parkinson's disease may be useful for screening therapeutics for neuroprotection in that disease stage. (Source: Molecular Neurodegeneration) Molecular Neurodegeneration journals http://www.medworm.com/rss/comments.php?id=2073351 Mon, 29 Dec 2008 05:00:00 +0100 2073351 http://www.medworm.com/index.php?rid=1894331&cid=s_34083_25_f&fid=34083&url=http%3A%2F%2Fwww.molecularneurodegeneration.com%2Fcontent%2F3%2F1%2F15 Conclusions: Our results suggest that Ca2+ and mitochondria stabilizing effects may, in part, be responsible for beneficial clinical effects of Dimebon. However, the high concentrations of Dimebon required to achieve Ca2+ stabilizing and neuroprotective effects in our in vitro studies (50 uM) indicate that properties of Dimebon as cognitive enhancer are most likely due to potent inhibition of H1 histamine receptors. It is also possible that Dimebon acts on novel high affinity targets not present in cultured MSN preparation. Unbiased evaluation of Dimebon against a set of biochemical targets indicated that Dimebon efficiently inhibited a number of additional receptors. Potential interactions with these receptors need to be considered in interpretation of results obtained with Dimebon in cl... Molecular Neurodegeneration journals http://www.medworm.com/rss/comments.php?id=1894331 Tue, 21 Oct 2008 04:00:00 +0100 1894331 http://www.medworm.com/index.php?rid=1894330&cid=s_34083_25_f&fid=34083&url=http%3A%2F%2Fwww.molecularneurodegeneration.com%2Fcontent%2F3%2F1%2F16 Conclusions: These data reveal the propensity of vitronectin to behave as an amyloid protein and put forth the possibilities that accumulation of misfolded vitronectin may contribute to aggregate formation seen in age-related amyloid diseases. (Source: Molecular Neurodegeneration) Molecular Neurodegeneration journals http://www.medworm.com/rss/comments.php?id=1894330 Tue, 21 Oct 2008 04:00:00 +0100 1894330 http://www.medworm.com/index.php?rid=1797613&cid=s_34083_25_f&fid=34083&url=http%3A%2F%2Fwww.molecularneurodegeneration.com%2Fcontent%2F3%2F1%2F12 Conclusion: Overall, these data suggest that the release of the APP intracellular domain may modulate the sensitivity of neuronal cells to toxic stimuli, and that a transcriptional role of AID could be inscribed in signaling pathways thatare not activated in basal conditions. (Source: Molecular Neurodegeneration) Molecular Neurodegeneration journals http://www.medworm.com/rss/comments.php?id=1797613 Tue, 02 Sep 2008 04:00:00 +0100 1797613 http://www.medworm.com/index.php?rid=1652106&cid=s_34083_25_f&fid=34083&url=http%3A%2F%2Fwww.molecularneurodegeneration.com%2Fcontent%2F3%2F1%2F9 In conclusion the activation of the Wnt signaling pathway could be proposed as a therapeutic target for the treatment of AD. (Source: Molecular Neurodegeneration) Molecular Neurodegeneration journals http://www.medworm.com/rss/comments.php?id=1652106 Thu, 24 Jul 2008 04:00:00 +0100 1652106 http://www.medworm.com/index.php?rid=1615383&cid=s_34083_25_f&fid=34083&url=http%3A%2F%2Fwww.molecularneurodegeneration.com%2Fcontent%2F3%2F1%2F7 Conclusion: Taken together, our results show genetically controlled distinct patterns of MOG and MAG depletion, in MOG35–55 induced EAE in H-2b and H-2b/s mice. The data also suggest distinctive immune regulation of acute lesions that develop in relapsing compared to disease onset. A profound depletion of MAG, concomitant with marked depletion of axonal NF160, and sharp elevation of PARPp85 levels, occurred exclusively in relapsing H-2b/s mice. Our findings suggest concurrence of sharp decrease of MAG levels, axonal dysfunction and irreversible apoptosis with severe relapsing disease in H-2b/s mice. We propose that MOG-induced EAE in H-2b/s mice may prove as a useful model in studying mechanisms, which govern autoimmune-induced preferential loss of MAG, and its impact on oligodendroglial... Molecular Neurodegeneration journals http://www.medworm.com/rss/comments.php?id=1615383 Mon, 09 Jun 2008 04:00:00 +0100 1615383 http://www.medworm.com/index.php?rid=1474759&cid=s_34083_25_f&fid=34083&url=http%3A%2F%2Fwww.molecularneurodegeneration.com%2Fcontent%2F3%2F1%2F6 This study provides an important structural clue for the rational design of drugs to inhibit processing of APP at the γ-site without interfering with Notch processing. (Source: Molecular Neurodegeneration) Molecular Neurodegeneration journals http://www.medworm.com/rss/comments.php?id=1474759 Mon, 12 May 2008 04:00:00 +0100 1474759 http://www.medworm.com/index.php?rid=1254953&cid=s_34083_25_f&fid=34083&url=http%3A%2F%2Fwww.molecularneurodegeneration.com%2Fcontent%2F3%2F1%2F4 Conclusion: Taken together, we have identified a novel brain-enriched RING finger E3 ligase, which was up regulated in AD brains and neuronal cells exposed to injurious insults. It interacted with ATP6V0C protein suggesting that it may play a very specific role in controlling the turnover of an essential component of neurotransmitter release machinery. (Source: Molecular Neurodegeneration) Molecular Neurodegeneration journals http://www.medworm.com/rss/comments.php?id=1254953 Mon, 25 Feb 2008 05:00:00 +0100 1254953 http://www.medworm.com/index.php?rid=1136412&cid=s_34083_25_f&fid=34083&url=http%3A%2F%2Fwww.molecularneurodegeneration.com%2Fcontent%2F3%2F1%2F2 The early embryonic lethality of mutant mice bearing germ-line deletions of both presenilin genes precluded the study of their functions in neural development. We therefore employed the Cre-loxP technology to generate presenilin conditional double knockout (PS cDKO) mice, in which expression of both presenilins is inactivated in neural progenitor cells (NPC) or neural stem cells and their derivative neurons and glia beginning at embryonic day 11 (E11). In PS cDKO mice, dividing NPCs labeled by BrdU are decreased in number beginning at E13.5. By E15.5, fewer than 20% of NPCs remain in PS cDKO mice. The depletion of NPCs is accompanied by severe morphological defects and hemorrhages in the PS cDKO embryonic brain. Interkinetic nuclear migration of NPCs is also disrupted in PS cDKO embryos, a... Molecular Neurodegeneration journals http://www.medworm.com/rss/comments.php?id=1136412 Tue, 08 Jan 2008 05:00:00 +0100 1136412 http://www.medworm.com/index.php?rid=1082024&cid=s_34083_25_f&fid=34083&url=http%3A%2F%2Fwww.molecularneurodegeneration.com%2Fcontent%2F2%2F1%2F23 Conclusions: Our results indicate that, in the HEK293 system, Munc13-1, Munc18, NSF, and EVE-1 fail to meet essential criteria for identity as PMES for APP. (Source: Molecular Neurodegeneration) Molecular Neurodegeneration journals http://www.medworm.com/rss/comments.php?id=1082024 Sun, 09 Dec 2007 05:00:00 +0100 1082024 http://www.medworm.com/index.php?rid=1029828&cid=s_34083_25_f&fid=34083&url=http%3A%2F%2Fwww.molecularneurodegeneration.com%2Fcontent%2F2%2F1%2F22 The pathogenesis of Alzheimer's disease is highly complex. While several pathologies characterize this disease, amyloid plaques, composed of the beta-amyloid peptide are hallmark neuropathological lesions in Alzheimer's disease brain. Indeed, a wealth of evidence suggests that beta-amyloid is central to the pathophysiology of AD and is likely to play an early role in this intractable neurodegenerative disorder. The BACE1 enzyme is essential for the generation of beta-amyloid. BACE1 knockout mice do not produce beta-amyloid and are free from Alzheimer's associated pathologies including neuronal loss and certain memory deficits. The fact that BACE1 initiates the formation of beta-amyloid, and the observation that BACE1 levels are elevated in this disease provide direct and compelling reasons... Molecular Neurodegeneration journals http://www.medworm.com/rss/comments.php?id=1029828 Thu, 15 Nov 2007 05:00:00 +0100 1029828 http://www.medworm.com/index.php?rid=991671&cid=s_34083_25_f&fid=34083&url=http%3A%2F%2Fwww.molecularneurodegeneration.com%2Fcontent%2F2%2F1%2F21 Conclusions: We have developed a QPCR genotyping method that permits rapid and effective genotyping of Wlds copy number. This technique will be of particular benefit in studies where Wlds mice are cross-bred with other mouse models of neurodegenerative disease in order to understand the neuroprotective processes conferred by the Wlds mutation. (Source: Molecular Neurodegeneration) Molecular Neurodegeneration journals http://www.medworm.com/rss/comments.php?id=991671 Tue, 30 Oct 2007 04:00:00 +0100 991671 http://www.medworm.com/index.php?rid=969859&cid=s_34083_25_f&fid=34083&url=http%3A%2F%2Fwww.molecularneurodegeneration.com%2Fcontent%2F2%2F1%2F20 Conclusions: The results show that LXR agonists could alleviate AD pathology by acting on amyloid deposition and brain inflammation. An increased understanding of the LXR controlled regulation of A-beta aggregation and clearance systems will lead to the development of more specific and powerful agonists targeting LXR for the treatment of AD. (Source: Molecular Neurodegeneration) Molecular Neurodegeneration journals http://www.medworm.com/rss/comments.php?id=969859 Mon, 22 Oct 2007 04:00:00 +0100 969859 http://www.medworm.com/index.php?rid=905844&cid=s_34083_25_f&fid=34083&url=http%3A%2F%2Fwww.molecularneurodegeneration.com%2Fcontent%2F2%2F1%2F18 Conclusions: Since the fibril specific antibodies are conformation dependent, sequence-independent, and recognize epitopes that are distinct from those present in prefibrillar oligomers, they may have broad utility for detecting and characterizing the accumulation of amyloid fibrils and fibrillar type oligomers in degenerative diseases. (Source: Molecular Neurodegeneration) Molecular Neurodegeneration journals http://www.medworm.com/rss/comments.php?id=905844 Wed, 26 Sep 2007 04:00:00 +0100 905844 http://www.medworm.com/index.php?rid=847112&cid=s_34083_25_f&fid=34083&url=http%3A%2F%2Fwww.molecularneurodegeneration.com%2Fcontent%2F2%2F1%2F17 Alzheimer's disease (AD) is characterized by the presence of two histopathological hallmarks; the senile plaques, or extracellular deposits mainly composed of amyloid-beta peptide (Abeta), and the neurofibrillary tangles, or intraneuronal inclusions composed of hyperphosphorylated tau protein. Since Abeta aggregates are found in the pathological cases, several strategies are under way to develop drugs that interact with Abeta to reduce its assembly. One of them is 3-amino-1 propane sulfonic acid (Tramiprosate, 3-APS, AlzhemedTM), that was developed as a sulfated glycosaminoglycan mimetic, that could interact with Abeta peptide, preventing its aggregation. However, little is known about the action of 3-APS on tau protein aggregation. In this work, we have tested the action of 3-APS on c... Molecular Neurodegeneration journals http://www.medworm.com/rss/comments.php?id=847112 Thu, 06 Sep 2007 04:00:00 +0100 847112 http://www.medworm.com/index.php?rid=820680&cid=s_34083_25_f&fid=34083&url=http%3A%2F%2Fwww.molecularneurodegeneration.com%2Fcontent%2F2%2F1%2F15 Conclusions: Taken together, we have shown that this screen can identify known APP metabolism regulators that control proteolysis, intracellular trafficking, maturation and levels of APP and its proteolytic products. We demonstrate for the first time that Ubiquilin 1 regulates APP metabolism in the human neuroblastoma cell line, SH-SY5Y. (Source: Molecular Neurodegeneration) Molecular Neurodegeneration journals http://www.medworm.com/rss/comments.php?id=820680 Fri, 24 Aug 2007 04:00:00 +0100 820680 http://www.medworm.com/index.php?rid=777229&cid=s_34083_25_f&fid=34083&url=http%3A%2F%2Fwww.molecularneurodegeneration.com%2Fcontent%2F2%2F1%2F14 Conclusion: These findings show that ApoER2 negatively affects APP internalization. However, ApoER2 expression stimulates Aβ production by shifting the proportion of APP from the non-rafts to the raft membrane domains, thereby promoting β-secretase and γ-secretase mediated amyloidogenic processing and also by incrementing the activity of γ-secretase. (Source: Molecular Neurodegeneration) Molecular Neurodegeneration journals http://www.medworm.com/rss/comments.php?id=777229 Mon, 09 Jul 2007 04:00:00 +0100 777229 http://www.medworm.com/index.php?rid=717877&cid=s_34083_25_f&fid=34083&url=http%3A%2F%2Fwww.molecularneurodegeneration.com%2Fcontent%2F2%2F1%2F13 John Finberg is a professor of pharmacology at the Faculty of Medicine, Technion - Israel Institute of Technology, home of Israel's two Nobel laureates. He and his colleague Prof. Moussa Youdim were instrumental in the early clinical development of the anti-Parkinson drug rasagiline, which gained UK- and EU-marketing authorization in 2005 and US FDA approval in 2006. In our interview, Finberg reflects on his clinical research to develop rasagiline as a commercial drug and its proposed pharmacological mechanisms of action. Moreover, he elucidates the current state of anti-Parkinson drug discovery and offers direction for future research. (Source: Molecular Neurodegeneration) Molecular Neurodegeneration journals http://www.medworm.com/rss/comments.php?id=717877 Fri, 06 Jul 2007 04:00:00 +0100 717877 http://www.medworm.com/index.php?rid=702975&cid=s_34083_25_f&fid=34083&url=http%3A%2F%2Fwww.molecularneurodegeneration.com%2Fcontent%2F2%2F1%2F12 Conclusions: These results suggest a new role for phosphorylation of tau by GSK-3beta and provide a new model system to study mechanisms of neurofibrillary tangle development. Although the severity of dementia has been found to correlate with the presence of NFT levels, there is some question as to the identity of the neurotoxic agents involved. This model system will be beneficial in identifying intermediates or side reaction products that might be neurotoxic. (Source: Molecular Neurodegeneration) Molecular Neurodegeneration journals http://www.medworm.com/rss/comments.php?id=702975 Thu, 28 Jun 2007 04:00:00 +0100 702975 http://www.medworm.com/index.php?rid=672231&cid=s_34083_25_f&fid=34083&url=http%3A%2F%2Fwww.molecularneurodegeneration.com%2Fcontent%2F2%2F1%2F11 Conclusions: The results show that AAV-mediated gene transfer is a valuable tool to model aspects of AD pathology in vivo, and demonstrate that whilst expression of Abeta42 alone is sufficient to initiate Abeta deposition, both Abeta40 and Abeta42 may contribute to cognitive deficits. (Source: Molecular Neurodegeneration) Molecular Neurodegeneration journals http://www.medworm.com/rss/comments.php?id=672231 Sat, 09 Jun 2007 04:00:00 +0100 672231 http://www.medworm.com/index.php?rid=644331&cid=s_34083_25_f&fid=34083&url=http%3A%2F%2Fwww.molecularneurodegeneration.com%2Fcontent%2F2%2F1%2F10 Parkinson's disease is the most common movement disorder characterized by dopaminergic dysfunction and degeneration. Loss-of-function mutations in the DJ-1 gene have been linked to autosomal recessive forms of early-onset familial Parkinson's disease. DJ-1 is thought to play roles in protection of cells against oxidative stress and in maintenance of the normal dopaminergic function in the nigrostriatal pathway. Here we investigate the consequence of both DJ-1 inactivation and aging in mice. We found that DJ-1-/- mice at the age of 24-27 months have normal numbers of dopaminergic neurons in the substantia nigra and normal levels of dopamine and its major metabolites in the striatum. The number of noradrenergic neurons in the locus coeruleus is also unchanged in DJ-1-/- mice. Moreover, there... Molecular Neurodegeneration journals http://www.medworm.com/rss/comments.php?id=644331 Tue, 29 May 2007 04:00:00 +0100 644331 http://www.medworm.com/index.php?rid=619670&cid=s_34083_25_f&fid=34083&url=http%3A%2F%2Fwww.molecularneurodegeneration.com%2Fcontent%2F2%2F1%2F9 Conclusions: These results suggest that although apoE and a lipid particle are lipid acceptors, when apoE and a lipid particle form a complex, apoE on the particle surface inhibits the lipid particle-mediated cholesterol release from cells in an apoE-concentration-dependent manner. (Source: Molecular Neurodegeneration) Molecular Neurodegeneration journals http://www.medworm.com/rss/comments.php?id=619670 Tue, 15 May 2007 04:00:00 +0100 619670 http://www.medworm.com/index.php?rid=579186&cid=s_34083_25_f&fid=34083&url=http%3A%2F%2Fwww.molecularneurodegeneration.com%2Fcontent%2F2%2F1%2F8 In conclusion, this study provides the first in vivo genetic evidence that pathological cell-cell interactions are necessary for striatal pathogenesis in a conditional mouse model of HD, and suggests a two-hit hypothesis in which both cell-autonomous toxicity and pathological cell-cell interactions are critical to HD pathogenesis. (Source: Molecular Neurodegeneration) Molecular Neurodegeneration journals http://www.medworm.com/rss/comments.php?id=579186 Mon, 30 Apr 2007 04:00:00 +0100 579186 http://www.medworm.com/index.php?rid=540463&cid=s_34083_25_f&fid=34083&url=http%3A%2F%2Fwww.molecularneurodegeneration.com%2Fcontent%2F2%2F1%2F7 Conclusions. We found that CSF apoE levels vary widely between individuals, but are stable within individuals over a two-week interval. AD status, APOE genotype, gender and race do not affect CSF apoE levels, but average CSF apoE levels increase with age. Given the lack of association between CSF apoE levels and genotypes for the ABCA1 SNPs we examined, either these SNPs do not affect ABCA1 function or if they do, they do not have strong effects in the CNS. Finally, we find no evidence for an association between the ABCA1 SNP rs2230806 and AD in a large sample set. (Source: Molecular Neurodegeneration) Molecular Neurodegeneration journals http://www.medworm.com/rss/comments.php?id=540463 Thu, 12 Apr 2007 04:00:00 +0100 540463 http://www.medworm.com/index.php?rid=476312&cid=s_34083_25_f&fid=34083&url=http%3A%2F%2Fwww.molecularneurodegeneration.com%2Fcontent%2F2%2F1%2F5 No abstract available (Source: Molecular Neurodegeneration) Molecular Neurodegeneration journals http://www.medworm.com/rss/comments.php?id=476312 Fri, 16 Mar 2007 04:00:00 +0100 476312 http://www.medworm.com/index.php?rid=476311&cid=s_34083_25_f&fid=34083&url=http%3A%2F%2Fwww.molecularneurodegeneration.com%2Fcontent%2F2%2F1%2F6 Alpha-synuclein is a small soluble, cytosolic protein which associates with vesicular membranes. It is a component of intracellular Lewy bodies present in Parkinsons disease and a subset of Alzheimers disease (AD). In addition, early studies identified a fragment of alpha-synuclein in the amyloid plaques of AD patients. Hypothesizing that alpha-synuclein might modify the AD pathogenic process, we crossed the Tg2576 strain of APP transgenic mice onto alpha-synuclein knockout background and determined the effects of alpha-synuclein on Abeta production and plaque deposition. We found that alpha-synuclein deficiency does not affect the Abeta levels, nor does it alter the age of onset of plaque pathology. To our surprise, however, loss of alpha-synuclein leads to a significant increase in plaqu... Molecular Neurodegeneration journals http://www.medworm.com/rss/comments.php?id=476311 Fri, 16 Mar 2007 04:00:00 +0100 476311 http://www.medworm.com/index.php?rid=405328&cid=s_34083_25_f&fid=34083&url=http%3A%2F%2Fwww.molecularneurodegeneration.com%2Fcontent%2F2%2F1%2F4 Conclusion: These data assign significance to p24 family proteins in regulating APP trafficking in the continuum of bidirectional transport between the ER and Golgi, and ascribe new relevance to the regulation of early trafficking in AD pathogenesis. (Source: Molecular Neurodegeneration) Molecular Neurodegeneration journals http://www.medworm.com/rss/comments.php?id=405328 Thu, 08 Feb 2007 07:00:00 +0100 405328 http://www.medworm.com/index.php?rid=403442&cid=s_34083_25_f&fid=34083&url=http%3A%2F%2Fwww.molecularneurodegeneration.com%2Fcontent%2F2%2F1%2F3 Conclusions: Our data suggest that APP-BP1 may inhibit Abeta42 production by interacting with PS1 under physiological conditions. (Source: Molecular Neurodegeneration) Molecular Neurodegeneration journals http://www.medworm.com/rss/comments.php?id=403442 Wed, 07 Feb 2007 07:00:00 +0100 403442 http://www.medworm.com/index.php?rid=440625&cid=s_34083_25_f&fid=34083&url=http%3A%2F%2Fwww.molecularneurodegeneration.com%2Fcontent%2F2%2F1%2F3 Conclusion: Our data suggest that APP-BP1 may inhibit Aβ42 production by interacting with PS1 under physiological conditions. (Source: Molecular Neurodegeneration) Molecular Neurodegeneration journals http://www.medworm.com/rss/comments.php?id=440625 Wed, 07 Feb 2007 05:00:00 +0100 440625 http://www.medworm.com/index.php?rid=373772&cid=s_34083_25_f&fid=34083&url=http%3A%2F%2Fwww.molecularneurodegeneration.com%2Fcontent%2F2%2F1%2F2 Conclusions: These data not only support the shared mechanistic involvement of free radical damage and inflammation in Alzheimer disease, but also indicate that multiple pathogenic "hits" are likely necessary for both the development and propagation of Alzheimer disease. (Source: Molecular Neurodegeneration) Molecular Neurodegeneration journals http://www.medworm.com/rss/comments.php?id=373772 Mon, 22 Jan 2007 07:00:00 +0100 373772 http://www.medworm.com/index.php?rid=362820&cid=s_34083_25_f&fid=34083&url=http%3A%2F%2Fwww.molecularneurodegeneration.com%2Fcontent%2F1%2F1%2F17 Conclusion: We conclude that LRRK2 is a component of Lewy bodies in both PD and DLB, and therefore plays an important role in the Lewy body formation and disease pathogenesis. Information on the cellular localization of LRRK2 under normal and pathological conditions will deepen our understanding of its functions and molecular pathways relevant to the progression of PD and related disorders. (Source: Molecular Neurodegeneration) Molecular Neurodegeneration journals http://www.medworm.com/rss/comments.php?id=362820 Thu, 30 Nov 2006 07:00:00 +0100 362820 http://www.medworm.com/index.php?rid=362821&cid=s_34083_25_f&fid=34083&url=http%3A%2F%2Fwww.molecularneurodegeneration.com%2Fcontent%2F1%2F1%2F16 Conclusion: Our FLIM data strongly suggest dimer formation between two separate SPP proteins. Although the tagged SPP constructs are expressed throughout the cell, SPP dimer detection by FLIM is seen predominantly at or near the plasma membrane. (Source: Molecular Neurodegeneration) Molecular Neurodegeneration journals http://www.medworm.com/rss/comments.php?id=362821 Tue, 14 Nov 2006 07:00:00 +0100 362821 http://www.medworm.com/index.php?rid=362822&cid=s_34083_25_f&fid=34083&url=http%3A%2F%2Fwww.molecularneurodegeneration.com%2Fcontent%2F1%2F1%2F15 More than a decade has passed since apolipoprotein E4 (APOE-ε4) was identified as a primary risk factor for Alzheimer 's disease (AD), yet researchers are even now struggling to understand how the apolipoprotein system integrates into the puzzle of AD etiology. The specific pathological actions of apoE4, methods of modulating apolipoprotein E4-associated risk, and possible roles of apoE in normal synaptic function are still being debated. These critical questions will never be fully answered without a complete understanding of the life cycle of the apolipoprotein receptors that mediate the uptake, signaling, and degradation of apoE. The present review will focus on apoE receptors as modulators of apoE actions and, in particular, explore the functions of soluble apoE receptors, a field alm... Molecular Neurodegeneration journals http://www.medworm.com/rss/comments.php?id=362822 Tue, 24 Oct 2006 06:00:00 +0100 362822 http://www.medworm.com/index.php?rid=362823&cid=s_34083_25_f&fid=34083&url=http%3A%2F%2Fwww.molecularneurodegeneration.com%2Fcontent%2F1%2F1%2F14 Conclusion: Therefore, our findings suggest that LH is not only able to bind to its receptor and induce potentially pathogenic signaling in AD, but also that steroidogenic pathways regulated by LH may play a role in AD. (Source: Molecular Neurodegeneration) Molecular Neurodegeneration journals http://www.medworm.com/rss/comments.php?id=362823 Tue, 03 Oct 2006 06:00:00 +0100 362823 http://www.medworm.com/index.php?rid=362824&cid=s_34083_25_f&fid=34083&url=http%3A%2F%2Fwww.molecularneurodegeneration.com%2Fcontent%2F1%2F1%2F12 Selenium is an essential micronutrient that function through selenoproteins. Selenium deficiency results in lower concentrations of selenium and selenoproteins. The brain maintains it's selenium better than other tissues under low-selenium conditions. Recently, the selenium-containing protein selenoprotein P (Sepp) has been identified as a possible transporter of selenium. The targeted disruption of the selenoprotein P gene (Sepp1) results in decreased brain selenium concentration and neurological dysfunction, unless selenium intake is excessive However, the effect of selenoprotein P deficiency on the processes of memory formation and synaptic plasticity is unknown. In the present studies Sepp1(-/-) mice and wild type littermate controls (Sepp1(+/+)) fed a high-selenium diet (1 mg Se/kg) w... Molecular Neurodegeneration journals http://www.medworm.com/rss/comments.php?id=362824 Tue, 19 Sep 2006 06:00:00 +0100 362824 http://www.medworm.com/index.php?rid=362825&cid=s_34083_25_f&fid=34083&url=http%3A%2F%2Fwww.molecularneurodegeneration.com%2Fcontent%2F1%2F1%2F11 Conclusion: Naturally occurring environmental RAD exposure may dramatically enhance AD deterioration by selectively targeting brain areas of emotions (Amy) and memory (Hip). (Source: Molecular Neurodegeneration) Molecular Neurodegeneration journals http://www.medworm.com/rss/comments.php?id=362825 Mon, 11 Sep 2006 06:00:00 +0100 362825