TFEB in Alzheimer's disease: From molecular mechanisms to therapeutic implications

被引:26
作者
Gu, Zhongya [1 ]
Cao, Huan [1 ]
Zuo, Chengchao [1 ]
Huang, Yaqi [1 ]
Miao, Jinfeng [1 ]
Song, Yu [1 ]
Yang, Yuyan [1 ]
Zhu, Liudi [1 ]
Wang, Furong [1 ]
机构
[1] Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Dept Neurol, 1095 Jiefang Rd, Wuhan 430030, Hubei, Peoples R China
基金
中国国家自然科学基金;
关键词
Alzheimer's disease; Transcription factor EB; Autophagy; Lysosome; A? plaque; Tau phosphorylation; TRANSCRIPTION FACTOR EB; REGULATING LYSOSOMAL BIOGENESIS; AMYLOID-BETA; A-BETA; COGNITIVE IMPAIRMENT; ALPHA-SECRETASE; MOUSE MODEL; SIGNALING PATHWAYS; AUTOPHAGY FLUX; TAU PATHOLOGY;
D O I
10.1016/j.nbd.2022.105855
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Alzheimer's disease (AD), an age-dependent neurodegenerative disorder, is the most prevalent neurodegenera-tive disease worldwide. The primary pathological hallmarks of AD are the deposition of beta-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 asso-ciated 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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页数:13
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