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

ABSTRACT: 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 ?-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.

SUBMITTER: Wang Z 

PROVIDER: S-EPMC7073207 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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A Curcumin Derivative Activates TFEB and Protects Against Parkinsonian Neurotoxicity <i>in</i> <i>Vitro</i>.

Wang Ziying Z   Yang Chuanbin C   Liu Jia J   Chun-Kit Tong Benjamin B   Zhu Zhou Z   Malampati Sandeep S   Gopalkrishnashetty Sreenivasmurthy Sravan S   Cheung King-Ho KH   Iyaswamy Ashok A   Su Chengfu C   Lu Jiahong J   Song Juxian J   Li Min M  

International journal of molecular sciences 20200222 4

<b>A</b>bstract<b>:</b> 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, accompani  ...[more]

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