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

doi:10.1016/j.bcp.2023.115698

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

Biochem Pharmacol. 2023 Sep:215:115698. doi: 10.1016/j.bcp.2023.115698. Epub 2023 Jul 22.

Authors

Lijuan Zhang¹, Zhijia Li², Lan Zhang³, Yuan Qin⁴, Dongke Yu⁵

Affiliations

¹ 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.
² Sichuan Engineering Research Center for Biomimetic Synthesis of Natural Drugs, School of Life Science and Engineering, Southwest Jiaotong University, Chengdu 610031, China.
³ Sichuan Engineering Research Center for Biomimetic Synthesis of Natural Drugs, School of Life Science and Engineering, Southwest Jiaotong University, Chengdu 610031, China. Electronic address: zhanglanx_9@126.com.
⁴ 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: qinyuan0203@163.com.
⁵ 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: kkygrace24@163.com.

PMID: 37482200
DOI: 10.1016/j.bcp.2023.115698

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.

Keywords: Autophagy; Human disease; Pharmacological modulator; TFEB.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Autophagy / physiology
Basic Helix-Loop-Helix Leucine Zipper Transcription Factors* / genetics
Basic Helix-Loop-Helix Leucine Zipper Transcription Factors* / metabolism
Cell Nucleus / metabolism
Gene Expression Regulation
Humans
Lysosomes / metabolism
Neurodegenerative Diseases* / drug therapy
Neurodegenerative Diseases* / genetics
Neurodegenerative Diseases* / metabolism

Substances

Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
TFEB protein, human