TY - JOUR
T1 - Transcription factor EB
T2 - an emerging drug target for neurodegenerative disorders
AU - Song, Ju Xian
AU - Liu, Jia
AU - Jiang, Yimin
AU - Wang, Zi Ying
AU - Li, Min
N1 - Funding Information:
This study was supported by the National Natural Science Foundation of China (NSFC-81703487, NSFC-81773926), the General Research Fund (HKBU12101417, HKBU12100618) and the Hong Kong Health and Medical Research Fund (HMRF17182541, HMRF17182551) from the Hong Kong Government, research funds from the Shenzhen Science and Technology Innovation Commission (SZSTI 201803023000787, JCYJ 20180302174028790, JCYJ20180507184656626), and research funds from Hong Kong Baptist University (RC-IRCs/17-18/03, RC-IRCMS/19-20/H02). We would like to thank Martha Dahlen for editing this manuscript.
Publisher copyright:
© 2020 Elsevier Ltd. All rights reserved
PY - 2021/1
Y1 - 2021/1
N2 - 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 TFEB-mediated 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.
AB - 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 TFEB-mediated 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.
UR - http://www.scopus.com/inward/record.url?scp=85095789396&partnerID=8YFLogxK
U2 - 10.1016/j.drudis.2020.10.013
DO - 10.1016/j.drudis.2020.10.013
M3 - Review article
C2 - 33099023
AN - SCOPUS:85095789396
SN - 1359-6446
VL - 26
SP - 164
EP - 172
JO - Drug Discovery Today
JF - Drug Discovery Today
IS - 1
ER -
