Transcription factor EB: an emerging drug target for neurodegenerative disorders

The discovery of transcription factor EB (TFEB) as a master regulator of the autophagy?lysosomal pathway (ALP) has triggered increasing numbers of studies that aim to explore the therapeutic potential of targeting TFEB to treat neurodegenerative disorders (NDs) such as Alzheimer?s disease and Parkinson?s disease. So far, the findings are exciting and promising. Here, we delineate the dysfunction of the TFEBmediated ALP in NDs, and we summarize small molecules that have been identified as TFEB activators, along with their protective effects in NDs. We discuss the molecular mechanisms and targets, and the pros and cons of these TFEB activators from the perspective of drug development. Specific and potent small-molecule TFEB activators with ideal brain bioavailability could provide a method for treating NDs.

Automated summary

TFEB as a master regulator of the autophagy-lysosomal pathway holds therapeutic potential for neurodegenerative disorders, with small molecules identified as TFEB activators showing promise in protecting against these diseases. Research is ongoing and the development of specific and potent TFEB activators with ideal brain bioavailability could provide a method for treating neurodegenerative disorders.