Dissecting the multifaced function of transcription factor EB (TFEB) in human diseases: From molecular mechanism to pharmacological modulation.

Lijuan Zhang, Zhijia Li, Lan Zhang, Yuan Qin, Dongke Yu

Journal: Biochemical pharmacology 2023;215():115698

PMID: 37482200

Full Text on Elsevier Science View on PubMed

Abstract

The transcription factor EB (TFEB) is a transcription factor of the MiT/TFE family that translocations from the cytoplasm to the nucleus in response to various stimuli, including lysosomal stress and nutrient starvation. By activating genes involved in lysosomal function, autophagy, and lipid metabolism, TFEB plays a crucial role in maintaining cellular homeostasis. Dysregulation of TFEB has been implicated in various diseases, including cancer, neurodegenerative diseases, metabolic diseases, cardiovascular diseases, infectious diseases, and inflammatory diseases. Therefore, modulating TFEB activity with agonists or inhibitors may have therapeutic potential. In this review, we reviewed the recently discovered regulatory mechanisms of TFEB and their impact on human diseases. Additionally, we also summarize the existing TFEB inhibitors and agonists (targeted and non-targeted) and discuss unresolved issues and future research directions in the field. In summary, this review sheds light on the crucial role of TFEB, which may pave the way for its translation from basic research to practical applications, bringing us closer to realizing the full potential of TFEB in various fields.

Address: Department of Pharmacy, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610072, China; Personalized Drug Therapy Key Laboratory of Sichuan Province, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610072, China.; Sichuan Engineering Research Center for Biomimetic Synthesis of Natural Drugs, School of Life Science and Engineering, Southwest Jiaotong University, Chengdu 610031, China.; Sichuan Engineering Research Center for Biomimetic Synthesis of Natural Drugs, School of Life Science and Engineering, Southwest Jiaotong University, Chengdu 610031, China. Electronic address: [email protected].; The Center of Gastrointestinal and Minimally Invasive Surgery, Department of General Surgery, The Third People's Hospital of Chengdu, The Affiliated Hospital of Southwest Jiaotong University, Chengdu 610031, China; Medical Research Center, The Third People's Hospital of Chengdu, The Affiliated Hospital of Southwest Jiaotong University, Chengdu 610031, China. Electronic address: [email protected].; Department of Pharmacy, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610072, China; Personalized Drug Therapy Key Laboratory of Sichuan Province, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610072, China. Electronic address: [email protected].

DOI: 10.1016/j.bcp.2023.115698

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MeSH Terms: Humans, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors, Autophagy, Cell Nucleus, Lysosomes, Gene Expression Regulation, Neurodegenerative Diseases