Proteostasis and neurodegeneration: a closer look at autophagy in Alzheimer's disease

被引:30
作者
Barmaki, Haleh [1 ]
Nourazarian, Alireza [2 ]
Khaki-Khatibi, Fatemeh [1 ]
机构
[1] Tabriz Univ Med Sci, Fac Med, Dept Biochem & Clin Labs, Tabriz, Iran
[2] Khoy Univ Med Sci, Dept Basic Med Sci, Khoy, Iran
关键词
Alzheimer's disease; proteostasis; autophagy; neurodegeneration; oxidative stress;
D O I
10.3389/fnagi.2023.1281338
中图分类号
R592 [老年病学]; C [社会科学总论];
学科分类号
03 ; 0303 ; 100203 ;
摘要
Alzheimer's disease (AD) is characterized by the accumulation of misfolded amyloid-beta and tau proteins. Autophagy acts as a proteostasis process to remove protein clumps, although it progressively weakens with aging and AD, thus facilitating the accumulation of toxic proteins and causing neurodegeneration. This review examines the impact of impaired autophagy on the progression of AD disease pathology. Under normal circumstances, autophagy removes abnormal proteins and damaged organelles, but any dysfunction in this process can lead to the exacerbation of amyloid and tau pathology, particularly in AD. There is increasing attention to therapeutic tactics to revitalize autophagy, including reduced caloric intake, autophagy-stimulating drugs, and genetic therapy. However, the translation of these strategies into clinical practice faces several hurdles. In summary, this review integrates the understanding of the intricate role of autophagy dysfunction in Alzheimer's disease progression and reinforces the promising prospects of autophagy as a beneficial target for treatments to modify the course of Alzheimer's disease.
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页数:11
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