Document Type

Journal Article

Authors

Ziying Wang, Mr. & Mrs. Ko Chi-Ming Centre for Parkinson’s Disease Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR and nstitute for Research and Continuing Education, Hong Kong Baptist University, Shenzhen, China
Chuanbin Yang, Mr. & Mrs. Ko Chi-Ming Centre for Parkinson’s Disease Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR and nstitute for Research and Continuing Education, Hong Kong Baptist University, Shenzhen, China
Jia Liu, Mr. & Mrs. Ko Chi-Ming Centre for Parkinson’s Disease Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR
Chun-Kit Tong, Mr. & Mrs. Ko Chi-Ming Centre for Parkinson’s Disease Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR and nstitute for Research and Continuing Education, Hong Kong Baptist University, Shenzhen, China
Zhou Zhu, Mr. & Mrs. Ko Chi-Ming Centre for Parkinson’s Disease Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR and nstitute for Research and Continuing Education, Hong Kong Baptist University, Shenzhen, China
Sandeep Malampati, Mr. & Mrs. Ko Chi-Ming Centre for Parkinson’s Disease Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR
Sravan Gopalkrishnashetty Sreenivasmurthy, Mr. & Mrs. Ko Chi-Ming Centre for Parkinson’s Disease Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR
King-Ho Cheung, Mr. & Mrs. Ko Chi-Ming Centre for Parkinson’s Disease Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR and nstitute for Research and Continuing Education, Hong Kong Baptist University, Shenzhen, China
Ashok Iyaswamy, Mr. & Mrs. Ko Chi-Ming Centre for Parkinson’s Disease Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR
Chengfu Su, Mr. & Mrs. Ko Chi-Ming Centre for Parkinson’s Disease Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR
Jiahong Lu, State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau SAR
Juxian Song, Mr. & Mrs. Ko Chi-Ming Centre for Parkinson’s Disease Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR and Medical College of Acupuncture-Moxibustion and Rehabilitation, Guangzhou University of Chinese Medicine, Guangzhou, China
Min Li, Mr. & Mrs. Ko Chi-Ming Centre for Parkinson’s Disease Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR and nstitute for Research and Continuing Education, Hong Kong Baptist University, Shenzhen, China

Department/Unit

School of Chinese Medicine

Language

English

Abstract

TFEB (transcription factor EB), which is a master regulator of autophagy and lysosome biogenesis, is considered to be a new therapeutic target for Parkinson’s disease (PD). However, only several small-molecule TFEB activators have been discovered and their neuroprotective effects in PD are unclear. In this study, a curcumin derivative, named E4, was identified as a potent TFEB activator. Compound E4 promoted the translocation of TFEB from cytoplasm into nucleus, accompanied by enhanced autophagy and lysosomal biogenesis. Moreover, TFEB knockdown effectively attenuated E4-induced autophagy and lysosomal biogenesis. Mechanistically, E4-induced TFEB activation is mainly through AKT-MTORC1 inhibition. In the PD cell models, E4 promoted the degradation of α-synuclein and protected against the cytotoxicity of MPP+ (1-methyl-4-phenylpyridinium ion) in neuronal cells. Overall, the TFEB activator E4 deserves further study in animal models of neurodegenerative diseases, including PD.

Keywords

TFEB, Parkinson’s disease, α-synuclein, curcumin derivatives, MTORC1

Publication Date

2-2020

Source Publication Title

International Journal of Molecular Sciences

Volume

21

Issue

4

Publisher

MDPI

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

DOI

10.3390/ijms21041515

Link to Publisher's Edition

https://doi.org/10.3390/ijms21041515

ISSN (print)

16616596

ISSN (electronic)

14220067

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