کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5500667 1534301 2017 39 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Can 'calpain-cathepsin hypothesis' explain Alzheimer neuronal death?
ترجمه فارسی عنوان
آیا می توان فرضیه کالپین-کاتهپسین را توضیح داد که مرگ عصبی آلزایمر را توضیح دهد؟
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی سالمندی
چکیده انگلیسی
Neurons are highly specialized post-mitotic cells, so their homeostasis and survival depend on the tightly-regulated, continuous protein degradation, synthesis, and turnover. In neurons, autophagy is indispensable to facilitate recycling of long-lived, damaged proteins and organelles in a lysosome-dependent manner. Since lysosomal proteolysis under basal conditions performs an essential housekeeping function, inhibition of the proteolysis exacerbates level of neurodegeneration. The latter is characterized by an accumulation of abnormal proteins or organelles within autophagic vacuoles which reveal as 'granulo-vacuolar degenerations' on microscopy. Heat-shock protein70.1 (Hsp70.1), as a means of molecular chaperone and lysosomal stabilizer, is a potent survival protein that confers neuroprotection against diverse stimuli, but its depletion induces neurodegeneration via autophagy failure. In response to hydroxynonenal generated from linoleic or arachidonic acids by the reactive oxygen species, a specific oxidative injury 'carbonylation' occurs at the key site Arg469 of Hsp70.1. Oxidative stress-induced carbonylation of Hsp70.1, in coordination with the calpain-mediated cleavage, leads to lysosomal destabilization/rupture and release of cathepsins with the resultant neuronal death. Hsp70.1 carbonylation which occurs anywhere in the brain is indispensable for neuronal death, but extent of calpain activation should be more crucial for determining the cell death fate. Importantly, not only acute ischemia during stroke but also chronic ischemia due to ageing may cause calpain activation. Here, role of Hsp70.1-mediated lysosomal rupture is discussed by comparing ischemic and Alzheimer neuronal death. A common neuronal death cascade may exist between cerebral ischemia and Alzheimer's disease.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Ageing Research Reviews - Brought to you by:GAYATRI VIDYA PARISHAD COLLEGE OF ENGINEERING for Women Renewal due by 31 Dec 2017
نویسندگان
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