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A Curcumin Derivative Activates TFEB and Protects Against Parkinsonian Neurotoxicity in Vitro

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....

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Detalles Bibliográficos
Autores principales: Wang, Ziying, Yang, Chuanbin, Liu, Jia, Chun-Kit Tong, Benjamin, Zhu, Zhou, Malampati, Sandeep, Gopalkrishnashetty Sreenivasmurthy, Sravan, Cheung, King-Ho, Iyaswamy, Ashok, Su, Chengfu, Lu, Jiahong, Song, Juxian, Li, Min
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7073207/
https://www.ncbi.nlm.nih.gov/pubmed/32098449
http://dx.doi.org/10.3390/ijms21041515
Descripción
Sumario: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.