分子伴侣介导的自噬在阿尔茨海默病中作用的研究进展

doi:10.3969/j.issn.1674-8115.2021.11.020

摘要/Abstract

摘要：

阿尔茨海默病（Alzheimer's disease，AD）是一种常见的神经系统退行性疾病，其主要病理变化是β淀粉样蛋白（amyloid β-protein，Aβ）大量堆积形成的老年斑（senile plaque，SP）和细胞内Tau蛋白（Tau protein）过度磷酸化积聚形成的神经原纤维缠结（neurofibrillary tangles，NFTs）。分子伴侣介导的自噬（chaperone-mediated autophagy，CMA）是一种选择性地将带有CMA基序的蛋白传递到溶酶体进行降解的过程。当自噬过程受损时，Aβ与异常磷酸化的Tau蛋白会大量堆积于神经元内，从而破坏细胞的正常功能并加速其死亡。相关研究表明，CMA是早期AD中异常蛋白质降解的重要途径，且该途径的失活可能在AD进展中发挥了重要作用。该文从CMA的概念、生理作用，CMA与AD的病理联系等方面进行综述，并对CMA途径的失活在AD中的作用进行详细阐述，以期为AD发病机制的研究及治疗提供新的思路。

关键词: 分子伴侣介导的自噬, 阿尔茨海默病, Tau蛋白, β淀粉样蛋白

Abstract:

Alzheimer's disease (AD) is a common neurodegenerative disease. Its main pathological change is senile plaque (SP) formed by massive accumulation of amyloid β-protein (Aβ) and neurofibrillary tangles (NFTs) formed by excessive phosphorylation and accumulation of Tau protein in cells. Chaperone-mediated autophagy (CMA) selectively transfers proteins with CMA motifs to lysosomes for degradation. When the autophagy process is impaired, Aβ and abnormal phosphorylated Tau protein will accumulate in neurons, which can destroy the normal function of cells and accelerate their death. Relevant studies have shown that CMA is an important pathway for abnormal protein degradation in early AD, and the inactivation of this pathway may play an important role in the progression of AD. This paper reviews the concept, and physiological role of CMA and the pathological relationship between CMA and AD, and elaborates the role of inactivation of CMA pathway in AD diseases, in order to provide new ideas for the research and treatment of AD pathogenesis.

Key words: chaperone-mediated autophagy (CMA), Alzheimer's disease (AD), Tau protein, amyloid β-protein (Aβ)

中图分类号:

R741.02

陈俊慧, 谷有全, 姚利和, 张薇, 王怀祥. 分子伴侣介导的自噬在阿尔茨海默病中作用的研究进展[J]. 上海交通大学学报(医学版), 2021, 41(11): 1529-1534.

Jun-hui CHEN, You-quan GU, Li-he YAO, Wei ZHANG, Huai-xiang WANG. Research progress of chaperone-mediated autophagy in Alzheimer's disease[J]. JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE), 2021, 41(11): 1529-1534.

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