摘要
阿尔茨海默病(AD)的发病机制包括异常错折叠蛋白、淀粉样蛋白(Aβprotein,Aβ)和τ蛋白的沉积。β包括老年性斑块和形成神经原纤维缠结的τ聚集体,两者都是AD的标志。自噬是细胞内聚集蛋白A、β和功能失调的主要保守途径。许多动物模型研究表明,自噬通常是对抗AD进展的保护因子,与细胞质内毒性A、β和τ聚集有关。自噬的上调也有利于AD的治疗。改善对调节自噬的信号通路的理解对于发展AD治疗至关重要。本文综述了自噬的细胞和分子机制、它们在AD发病机制中的作用以及目前的药物发现策略。
关键词: 阿尔茨海默病,自噬,τ,淀粉样β蛋白,自噬体,治疗。
Current Alzheimer Research
Title:The Implications of Autophagy in Alzheimer’s Disease
Volume: 15 Issue: 14
关键词: 阿尔茨海默病,自噬,τ,淀粉样β蛋白,自噬体,治疗。
摘要: The pathogenic mechanisms of Alzheimer’s Disease (AD) involve the deposition of abnormally misfolded proteins, amyloid β protein (Aβ) and tau protein. Aβ comprises senile plaques, and tau aggregates form Neurofibrillary Tangles (NFTs), both of which are hallmarks of AD. Autophagy is the main conserved pathway for the degeneration of aggregated proteins, Aβ, tau and dysfunctional organelles in the cell. Many animal model studies have demonstrated that autophagy normally functions as the protective factor against AD progression associated with intracytoplasmic toxic Aβ and tau aggregates. The upregulation of autophagy can also be favorable in AD treatment. An improved understanding of the signaling pathways that regulate autophagy is critical to developing AD treatments. The cellular and molecular machineries of autophagy, their function in the pathogenesis of AD, and current drug discovery strategies will be discussed in this review.
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Cite this article as:
The Implications of Autophagy in Alzheimer’s Disease, Current Alzheimer Research 2018; 15 (14) . https://dx.doi.org/10.2174/1567205015666181004143432
DOI https://dx.doi.org/10.2174/1567205015666181004143432 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
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