کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1906254 1534883 2014 13 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Neurodegenerative disorders: Dysregulation of a carefully maintained balance?
ترجمه فارسی عنوان
اختلالات نوروژنراتیو: اختلال در تعادل دقیق نگهدارنده
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی سالمندی
چکیده انگلیسی


• Many different proteins are involved in aggregation formation.
• Amyloid formation is, to a certain extent, physiological.
• Protein aggregation can be protective against cell death.
• Loss of cellular equilibrium leads to multisystem failures.
• Disruption of homeostasis underlies neuronal degeneration.

The aggregation of misfolded proteins has long been regarded as a pathological event in neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease and Huntington's disease. However, the exact molecular mechanisms that govern protein metabolism that may lead to toxicity remain largely unclear. Originally targeted as the causative agent, it has since become evident that aggregation formation may not be necessary for disease progression and studies show that they may even serve functional and protective roles. Although the focus has since shifted to the toxicity of intermediate protein species preceding aggregation formation, many questions remain: Is the blame for the neural destruction to be put on one event alone, or rather on a state of cellular disequilibrium resulting from multiple events? If the cause is multifactorial, then what triggers the toxic cascade and how can this be targeted therapeutically? In order to understand the origin of toxicity, the exact underlying mechanism and impact of each contributing process must be assessed. Therefore, the structural properties, mechanism of formation, cytotoxic and/or protective effects, as well as the clinical impact of protein intermediates and aggregates will be reviewed here with the goal to establish a neurodegenerative disease model aimed at improving current therapeutics, which may ultimately contribute towards improved treatment modalities.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Experimental Gerontology - Volume 58, October 2014, Pages 279–291
نویسندگان
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