期刊
DRUG DISCOVERY TODAY
卷 26, 期 1, 页码 164-172出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.drudis.2020.10.013
关键词
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资金
- National Natural Science Foundation of China [NSFC81703487, NSFC81773926]
- Hong Kong Health and Medical Research Fund from the Hong Kong Government [HMRF17182541, HMRF17182551]
- Shenzhen Science and Technology Innovation Commission [SZSTI 201803023000787, JCYJ 20180302174028790, JCYJ20180507184656626]
- Hong Kong Baptist University [RCIRCs/1718/03, RCIRCMS/1920/H02]
- General Research Fund from the Hong Kong Government [HKBU12101417, HKBU12100618]
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.
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.
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