Session Information
Date: Tuesday, June 21, 2016
Session Title: Parkinson's disease: Pathophysiology
Session Time: 12:30pm-2:00pm
Location: Exhibit Hall located in Hall B, Level 2
Objective: Our previous study has demonstrated that resveratrol (RV) enhanced clearance of misfolded α-synuclein proteins in cellular models of PD, with the activation of SIRT1 and induction of autophagy. However, the SIRT1-dependent neuroprotective effect of RV in PD has not been demonstrated in vivo and further investigations are warranted to uncover the precise action mechanism for induction of autophagy by SIRT1.
Background: The accumulation of misfolded α-synuclein in dopamine (DA) neurons has emerged as a leading cause of neurodegeneration in Parkinson’s disease (PD). Studies have indicated that enhanced clearance of misfolded or aggregated proteins via autophagy might be promising in preventing or slowing down the degeneration process of PD.
Results: In this study, we found that MPTP-induced mouse model of PD exhibited behavioral impairment in open field test, stride length test and pole test, with the loss of DA neurons and the decreased levels of DA and TH protein. Administration of RV, a SIRT1 activator, significantly attenuated MPTP-induced behavioral impairment and neuronal damage, whereas treatment with EX527, a selective SIRT1 inhibitor, blocked the neuroprotective effect of RV on MPTP mice. Furthermore, we demonstrated that activation of SIRT1 by RV resulted in LC3 deacetylation, leading to LC3 redistributing from the nucleus to the cytoplasm and improving autophagic degradation of misfolded α-synuclein in DA neurons.
Conclusions: The present study provides in vivo evidences that RV may elicit neuroprotective effects in preventing or slowing down the degeneration process of PD. Deacetylation of LC3 by SIRT1 might be an important mechanism that RV exerts neuroprotective effects. Further detailed studies of LC3 deacetylation by SIRT1 would aid in the development of novel neuroprotective strategies for PD.
To cite this abstract in AMA style:
Y. Wu, Y. Guo, S. Dong, X. Cui, Y. Feng, W. Zhao. LC3 deacetylation by SIRT1 is involved in neuroprotective effects of resveratrol in an MPTP mouse model of Parkinson’s disease [abstract]. Mov Disord. 2016; 31 (suppl 2). https://www.mdsabstracts.org/abstract/lc3-deacetylation-by-sirt1-is-involved-in-neuroprotective-effects-of-resveratrol-in-an-mptp-mouse-model-of-parkinsons-disease/. Accessed May 14, 2025.« Back to 2016 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/lc3-deacetylation-by-sirt1-is-involved-in-neuroprotective-effects-of-resveratrol-in-an-mptp-mouse-model-of-parkinsons-disease/