TFEB
自噬
蛋白质稳态
碱性螺旋-环-螺旋-亮氨酸拉链转录因子
神经科学
溶酶体
生物
发病机制
细胞生物学
转录因子
免疫学
遗传学
基因
DNA结合蛋白
细胞凋亡
生物化学
酶
作者
Zhongya Gu,Huấn Cao,Chengchao Zuo,Yaqi Huang,Jinfeng Miao,Yu Song,Yuyan Yang,Liudi Zhu,Furong Wang
标识
DOI:10.1016/j.nbd.2022.105855
摘要
Alzheimer's disease (AD), an age-dependent neurodegenerative disorder, is the most prevalent neurodegenerative disease worldwide. The primary pathological hallmarks of AD are the deposition of β-amyloid plaques and neurofibrillary tangles. Autophagy, a pathway of clearing damaged organelles, macromolecular aggregates, and long-lived proteins via lysosomal degradation, has emerged as critical for proteostasis in the central nervous system (CNS). Studies have demonstrated that defective autophagy is strongly implicated in AD pathogenesis. Transcription factor EB (TFEB), a master transcriptional regulator of autophagy, enhances the expression of related genes that control autophagosome formation, lysosome function, and autophagic flux. The study of TFEB has greatly increased over the last decade, and the dysfunction of TFEB has been reported to be strongly associated with the pathogenesis of many neurodegenerative disorders, including AD. Here, we delineate the basic understanding of TFEB dysregulation involved in AD pathogenesis, highlighting the existing work that has been conducted on TFEB-mediated autophagy in neurons and other nonneuronal cells in the CNS. Additionally, we summarize the small molecule compounds that target TFEB-regulated autophagy involved in AD therapy. Our review may yield new insights into therapeutic approaches by targeting TFEB and provide a broadly applicable basis for the clinical treatment of AD.
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