Resveratrol alleviates MPTP-induced motor impairments and pathological changes by autophagic degradation of α-synuclein via SIRT1-deacetylated LC3.

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Resveratrol alleviates MPTP-induced motor impairments and pathological changes by autophagic degradation of α-synuclein via SIRT1-deacetylated LC3.

Mol Nutr Food Res. 2016 Oct;60(10):2161-2175

Authors: Guo YJ, Dong SY, Cui XX, Feng Y, Liu T, Yin M, Kuo SH, Tan EK, Zhao WJ, Wu YC

Abstract
SCOPE: The accumulation of misfolded α-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 α-synuclein in dopaminergic neurons. Furthermore, EX527 antagonized the neuroprotective effects of RV by reducing LC3 deacetylation and subsequent autophagic degradation of α-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 α-synuclein. Our observations suggest that RV may be a potential prophylactic and/or therapeutic agent for PD.

PMID: 27296520 [PubMed - indexed for MEDLINE]

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