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GSK-3β inhibition by curcumin mitigates amyloidogenesis via TFEB activation and anti-oxidative activity in human neuroblastoma cells

Cited 3 time in Web of Science Cited 3 time in Scopus
Authors
Song, Hyun-Chul; Chen, Yubing; Chen, Yingqing; Park, Jeongmin; Zheng, Min; Surh, Young-Joon; Kim, Uh-Hyun; Park, Jeong Woo; Yu, Rina; Chung, Hun Taeg; Joe, Yeonsoo
Issue Date
2020-07
Citation
Free Radical Research, pp.1-13
Keywords
Autophagyneurodegenerative diseasesheme oxygenase-1Alzheimer's DiseaseParkinson's Disease
Abstract
© 2020 Informa UK Limited, trading as Taylor & Francis Group.The translocation of transcription factor EB (TFEB) to the nucleus plays a pivotal role in the regulation of basic cellular processes, such as lysosome biogenesis and autophagy. Autophagy is an intracellular degradation system that delivers cytoplasmic constituents to the lysosome, which is important in maintaining cellular homeostasis during environmental stress. Furthermore, oxidative stress is a critical cause for the progression of neurodegenerative diseases. Curcumin has anti-oxidative and anti-inflammatory activities, and is expected to have potential therapeutic effects in various diseases. In this study, we demonstrated that curcumin regulated TFEB export signalling via inhibition of glycogen synthase kinase-3β (GSK-3β); GSK-3β was inactivated by curcumin, leading to reduced phosphorylation of TFEB. We further showed that H2O2-induced oxidative stress was reduced by curcumin via the Nrf2/HO-1 pathway in human neuroblastoma cells. In addition, we showed that curcumin induced the degradation of amyloidogenic proteins, including amyloid-β precursor protein and α-synuclein, through the TFEB-autophagy/lysosomal pathway. In conclusion, curcumin regulates autophagy by controlling TFEB through the inhibition of GSK-3β, and increases antioxidant gene expression in human neuroblastoma cells. These results contribute to the development of novel cellular therapies for neurodegenerative diseases.
ISSN
1071-5762
URI
https://hdl.handle.net/10371/172730
DOI
https://doi.org/10.1080/10715762.2020.1791843
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Graduate School of Convergence Science and Technology (융합과학기술대학원)Dept. of Molecular and Biopharmaceutical Sciences (분자의학 및 바이오제약학과)Journal Papers (저널논문_분자의학 및 바이오제약학과)
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