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A curcumin derivative activates TFEB and protects against parkinsonian neurotoxicity in vitro
Wang,Ziying1,2; Yang,Chuanbin1,2; Liu,Jia1; Tong,Benjamin Chun Kit1,2; Zhu,Zhou1,2; Malampati,Sandeep1; Sreenivasmurthy,Sravan Gopalkrishnashetty1; Cheung,King Ho1,2; Iyaswamy,Ashok1; Su,Chengfu1; Lu,Jiahong3; Song,Juxian1,4; Li,Min1,2
Source PublicationInternational Journal of Molecular Sciences

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.

KeywordCurcumin Derivatives Mtorc1 Parkinson’s Disease Tfeb Α-synuclein
URLView the original
Indexed BySCIE
WOS Research AreaBiochemistry & Molecular Biology ; Chemistry
WOS SubjectBiochemistry & Molecular Biology ; Chemistry, Multidisciplinary
WOS IDWOS:000522524400342
Scopus ID2-s2.0-85079840772
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Cited Times [WOS]:20   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Corresponding AuthorSong,Juxian; Li,Min
Affiliation1.Mr. & Mrs. Ko Chi-Ming Centre for Parkinson’s Disease Research,School of Chinese Medicine,Hong Kong Baptist University,Hong Kong
2.Institute for Research and Continuing Education,Hong Kong Baptist University,Shenzhen,518000,China
3.State Key Laboratory of Quality Research in Chinese Medicine,Institute of Chinese Medical Sciences,University of Macau,Macao
4.Medical College of Acupuncture-Moxibustion and Rehabilitation,Guangzhou University of Chinese Medicine,Guangzhou,510000,China
Recommended Citation
GB/T 7714
Wang,Ziying,Yang,Chuanbin,Liu,Jia,et al. A curcumin derivative activates TFEB and protects against parkinsonian neurotoxicity in vitro[J]. International Journal of Molecular Sciences,2020,21(4).
APA Wang,Ziying,Yang,Chuanbin,Liu,Jia,Tong,Benjamin Chun Kit,Zhu,Zhou,Malampati,Sandeep,Sreenivasmurthy,Sravan Gopalkrishnashetty,Cheung,King Ho,Iyaswamy,Ashok,Su,Chengfu,Lu,Jiahong,Song,Juxian,&Li,Min.(2020).A curcumin derivative activates TFEB and protects against parkinsonian neurotoxicity in vitro.International Journal of Molecular Sciences,21(4).
MLA Wang,Ziying,et al."A curcumin derivative activates TFEB and protects against parkinsonian neurotoxicity in vitro".International Journal of Molecular Sciences 21.4(2020).
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