Journal
MOLECULAR NUTRITION & FOOD RESEARCH
Volume 60, Issue 10, Pages 2161-2175Publisher
WILEY-BLACKWELL
DOI: 10.1002/mnfr.201600111
Keywords
alpha-synuclein; LC3 deacetylation; Parkinson's disease; Resveratrol; SIRT1
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Funding
- National Natural Science Foundation of China [81171205, 81371410, 81471232]
- Biomedical Multidisciplinary Program of Shanghai Jiao Tong University [YG2014MS31]
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Scope: The accumulation of misfolded alpha-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 alpha-synuclein in dopaminergic neurons. Furthermore, EX527 antagonized the neuroprotective effects of RV by reducing LC3 deacetylation and subsequent autophagic degradation of alpha-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 alpha-synuclein. Our observations suggest that RV may be a potential prophylactic and/or therapeutic agent for PD.
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