کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8263517 | 1534873 | 2015 | 5 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Senescence may mediate conversion of tau phosphorylation-induced apoptotic escape to neurodegeneration
ترجمه فارسی عنوان
زایمان ممکن است تبدیل فرار آپوپتوتیزم ناشی از فسفریلاسیون توا به تولید عصبی
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کلمات کلیدی
بیماری آلزایمر، تاو، هیپرفسفریلاسیون، آپوپتوز زناشویی، عصب مغزی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
سالمندی
چکیده انگلیسی
Neurodegeneration is the characteristic pathology in the brains of Alzheimer's disease (AD). However, the nature and molecular mechanism leading to the degeneration are not clarified. Given that only the neurons filled with neurofibrillary tangles survive to the end stage of the disease and the major component of the tangles is the hyperphosphorylated tau proteins, it is conceivable that tau hyperphosphorylation must play a crucial role in AD neurodegeneration. We have demonstrated that tau hyperphosphorylation renders the cells more resistant to the acute apoptosis. The molecular mechanisms involve substrate competition of tau and β-catenin for glycogen synthase kinase 3β (GSK-3β); activation of Akt; preservation of Bcl-2 and suppression of Bax, cytosolic cytochrome-c, and caspase-3 activity; and upregulation of unfolded protein response (UPR), i.e., up-regulating phosphorylation of PERK, eIF2 and IRE1 with an increased cleavage of ATF6 and ATF4. On the other hand, tau hyperphosphorylation promotes its intracellular accumulation and disrupts axonal transport; hyperphosphorylated tau also impairs cholinergic function and inhibits proteasome activity. These findings indicate that tau hyperphosphorylation and its intracellular accumulation play dual role in the evolution of AD. We speculate that transient tau phosphorylation helps cells abort from an acute apoptosis, while persistent tau hyperphosphorylation/accumulation may trigger cell senescence that eventually causes a chronic neurodegeneration. Therefore, the nature of “AD neurodegeneration” may represent a new type of tau-regulated chronic neuron death; and the stage of cell senescence may provide a broad window for the intervention of AD.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Experimental Gerontology - Volume 68, August 2015, Pages 82-86
Journal: Experimental Gerontology - Volume 68, August 2015, Pages 82-86
نویسندگان
Jian-Zhi Wang, Zhi-Hao Wang,