The regulatory mechanism and therapeutic potential of transcription factor EB in neurodegenerative diseases

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.

Automated summary

This review discusses the regulation and functions of transcription factor EB (TFEB) in the autophagy-lysosomal pathway (ALP), as well as its role in various neurodegenerative diseases. The protective effects and molecular mechanisms of TFEB-targeted agonists in neurodegeneration are summarized, and the pros and cons of these agonists in the treatment of neurodegenerative diseases are analyzed from the perspective of drug development. Further studies on the regulatory mechanisms of TFEB in other biological processes will enhance our understanding of the application of TFEB-targeted therapy in neurodegeneration.