کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
9880419 1535228 2005 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Cholesterol homeostasis failure as a unifying cause of synaptic degeneration
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی سالمندی
پیش نمایش صفحه اول مقاله
Cholesterol homeostasis failure as a unifying cause of synaptic degeneration
چکیده انگلیسی
We previously showed that fine tuning of neural cholesterol dynamics is essential for basic synapse function, plasticity and behavior. Significant experimental evidence indicates that cholinergic function, ionotropic and metabotropic receptor machinery, excessive tau phosphorylation, the change of amyloid beta (Abeta or Aβ) biochemistry, neural oxidative stress reactions, and other features of neurodegeneration also depend on fine tuning of brain cholesterol homeostasis. This evidence suggest that (i) cholesterol homeostasis break is the unifying primary cause of sporadic and familial Alzheimer's disease (AD), neuromuscular diseases (particularly inclusion-body myositis), Niemann-Pick's type C disease and Down syndrome, and (ii) explains the overlap of neurodegenerative hallmarks across the spectrum of neurodegenerative diseases. Provided is evidence-based explanation of why extremely rare (but scientifically popular) cases of AD associated with mutations in amyloid beta protein precursor (APP) and presenilin (PS) genes, are translated into the disorder via membrane cholesterol sensitivity of APP processing by secretases and Aβ generation. The reciprocal effect of Aβ on cholesterol synthesis, cellular uptake, efflux and esterification is summarized, as well as the potential implication of such biological function for the compensatory Aβ-assisted restoration of the synaptic long-term potentiation (LTP) and resulting inability of tackling amyloid to cure AD.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of the Neurological Sciences - Volumes 229–230, 15 March 2005, Pages 233-240
نویسندگان
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