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Title: Resveratrol alleviates MPTP-induced motor impairments and pathological changes by autophagic degradation of ?-synuclein via SIRT1-deacetylated LC3
Authors: Guo Y.-J.
Dong S.-Y.
Cui X.-X.
Feng Y.
Liu T.
Yin M.
Kuo S.-H.
Tan E.-K. 
Zhao W.-J.
Wu Y.-C.
Keywords: LC3 deacetylation
Parkinson's disease
Issue Date: 2016
Publisher: Wiley
Citation: Guo Y.-J., Dong S.-Y., Cui X.-X., Feng Y., Liu T., Yin M., Kuo S.-H., Tan E.-K., Zhao W.-J., Wu Y.-C. (2016). Resveratrol alleviates MPTP-induced motor impairments and pathological changes by autophagic degradation of ?-synuclein via SIRT1-deacetylated LC3. Molecular nutrition & food research 60 (10) : 2161-2175. ScholarBank@NUS Repository.
Abstract: SCOPE: The accumulation of misfolded ?-synuclein in dopaminergic neurons is the leading cause of Parkinson's disease (PD). Resveratrol (RV), a polyphenolic compound derived from grapes and red wine, exerts a wide range of beneficial effects via activation of sirtuin 1 (SIRT1) and induction of vitagenes. Here, we assessed the role of RV in a 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) induced mouse model of PD and explored its potential mechanisms.METHODS AND RESULTS: RV and EX527, a specific inhibitor of SIRT1, were administered before and after MPTP treatment. RV protected against MPTP-induced loss of dopaminergic neurons, and decreases in tyrosine hydroxylase and dopamine levels, as well as behavioral impairments. Meanwhile, RV administration activated SIRT1. Microtubule-associated protein 1 light chain 3 (LC3) was then deacetylated and redistributed from the nucleus to the cytoplasm, which provoked the autophagic degradation of ?-synuclein in dopaminergic neurons. Furthermore, EX527 antagonized the neuroprotective effects of RV by reducing LC3 deacetylation and subsequent autophagic degradation of ?-synuclein.CONCLUSION: We showed that RV ameliorated both motor deficits and pathological changes in MPTP-treated mice via activation of SIRT1 and subsequent LC3 deacetylation-mediated autophagic degradation of ?-synuclein. Our observations suggest that RV may be a potential prophylactic and/or therapeutic agent for PD. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Source Title: Molecular nutrition & food research
ISSN: 16134133
DOI: 10.1002/mnfr.201600111
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