School of Chinese Medicine
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.
TFEB, Parkinson’s disease, α-synuclein, curcumin derivatives, MTORC1
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International Journal of Molecular Sciences
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Wang, Z., Yang, C., Liu, J., Tong, C., Zhu, Z., Malampati, S., Sreenivasmurthy, S., Cheung, K., Iyaswamy, A., Su, C., Lu, J., Song, J., & Li, M. (2020). A Curcumin Derivative Activates TFEB and Protects Against Parkinsonian Neurotoxicity in Vitro. International Journal of Molecular Sciences, 21 (4). https://doi.org/10.3390/ijms21041515