School of Mental Health, Jining Medical University, Jining, China.
Shandong Key Laboratory of Behavioral Medicine, School of Mental Health, Jining Medical University, Jining, China.
CNS Neurosci Ther. 2023 Jan;29(1):37-59. doi: 10.1111/cns.13985. Epub 2022 Oct 2.
The autophagy-lysosomal pathway (ALP) is involved in the degradation of protein aggregates and damaged organelles. Transcription factor EB (TFEB), a major regulator of ALP, has emerged as a leading factor in addressing neurodegenerative disease pathology, including Alzheimer's disease (AD), Parkinson's disease (PD), PolyQ diseases, and Amyotrophic lateral sclerosis (ALS). In this review, we delineate the regulation of TFEB expression and its functions in ALP. Dysfunctions of TFEB and its role in the pathogenesis of several neurodegenerative diseases are reviewed. We summarize the protective effects and molecular mechanisms of some TFEB-targeted agonists in neurodegenerative diseases. We also offer our perspective on analyzing the pros and cons of these agonists in the treatment of neurodegenerative diseases from the perspective of drug development. More studies on the regulatory mechanisms of TFEB in other biological processes will aid our understanding of the application of TFEB-targeted therapy in neurodegeneration.
自噬溶酶体途径（ALP）参与蛋白质聚集体和受损细胞器的降解。转录因子 EB（TFEB）是 ALP 的主要调节因子，它已成为解决神经退行性疾病病理学的主要因素，包括阿尔茨海默病（AD）、帕金森病（PD）、PolyQ 疾病和肌萎缩侧索硬化症（ALS）。在这篇综述中，我们描述了 TFEB 表达的调节及其在 ALP 中的功能。我们回顾了 TFEB 的功能障碍及其在几种神经退行性疾病发病机制中的作用。我们总结了一些 TFEB 靶向激动剂在神经退行性疾病中的保护作用和分子机制。我们还从药物开发的角度分析了这些激动剂在治疗神经退行性疾病中的优缺点。更多关于 TFEB 在其他生物过程中的调节机制的研究将有助于我们理解 TFEB 靶向治疗在神经退行性疾病中的应用。
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