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A Review of APOE Genotype-Dependent Autophagic Flux Regulation in Alzheimer’s Disease
Journal of Alzheimer’s Disease ( IF 4 ) Pub Date : 2021-09-22 , DOI: 10.3233/jad-210602
Huiyi Chen 1, 2 , Feng Chen 1 , Miaoping Zhang 1 , Yanting Chen 1 , Lili Cui 1 , Chunmei Liang 1
Affiliation  

Autophagy is a basic physiological process maintaining cell renewal, the degradation of dysfunctional organelles, and the clearance of abnormal proteins and has recently been identified as a main mechanism underlying the onset and progression of Alzheimer’s disease (AD). The APOE ɛ4 genotype is thestrongest genetic determinant of AD pathogenesis and initiates autophagic flux at different times. This review synthesizes the current knowledge about the potential pathogenic effects of ApoE4 on autophagy and describes its associations with the biological hallmarks of autophagy and AD from a novel perspective. Via a remarkable variety of widely accepted signaling pathway markers, such as mTOR, TFEB, SIRT1, LC3, p62, LAMP1, LAMP2, CTSD, Rabs, and V-ATPase, ApoE isoforms differentially modulate autophagy initiation; membrane expansion, recruitment, and enclosure; autophagosome and lysosome fusion; and lysosomal degradation. Although the precise pathogenic mechanism varies for different genes and proteins, the dysregulation of autophagic flux is a key mechanism on which multiple pathogenic processes converge.

中文翻译:

阿尔茨海默病中 APOE 基因型依赖性自噬通量调节的综述

自噬是维持细胞更新、功能失调细胞器降解和异常蛋白质清除的基本生理过程,最近已被确定为阿尔茨海默病 (AD) 发病和进展的主要机制。APOE ɛ4 基因型是 AD 发病机制的最强遗传决定因素,并在不同时间启动自噬通量。这篇综述综合了目前关于 ApoE4 对自噬的潜在致病作用的知识,并从一个新的角度描述了它与自噬和 AD 的生物学特征的关联。通过多种广泛接受的信号通路标志物,例如 mTOR、TFEB、SIRT1、LC3、p62、LAMP1、LAMP2、CTSD、Rabs 和 V-ATPase,ApoE 亚型差异调节自噬起始;膜扩张,募集,和外壳;自噬体和溶酶体融合;和溶酶体降解。尽管不同基因和蛋白质的确切致病机制各不相同,但自噬通量的失调是多种致病过程汇聚的关键机制。
更新日期:2021-09-24
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