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Resveratrol-Activated AMPK/SIRT1/Autophagy in Cellular Models of Parkinson’s DiseaseWu Y.a–c · Li X.d · Zhu J.X.b · Xie W.b · Le W.b · Fan Z.d · Jankovic J.b, c · Pan T.b, e
aDepartment of Neurology, Shanghai First People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; bDepartment of Neurology, Parkinson’s Disease Research Laboratory, cDepartment of Neurology, Parkinson’s Disease Center and Movement Disorder Clinic, Baylor College of Medicine, and dDepartment of Experimental Therapeutics, M.D. Anderson Cancer Center, Houston, Tex., and eDiana Helis Henry Medical Research Foundation, New Orleans, La., USA Corresponding Author
Dr. Tianhong Pan
Parkinson Disease Research Laboratory
Department of Neurology, Baylor College of Medicine
One Baylor Plaza, MS NB302, Houston, TX 77030 (USA)
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Excessive misfolded proteins and/or dysfunctional mitochondria, which may cause energy deficiency, have been implicated in the etiopathogenesis of Parkinson’s disease (PD). Enhanced clearance of misfolded proteins or injured mitochondria via autophagy has been reported to have neuroprotective roles in PD models. The fact that resveratrol is a known compound with multiple beneficial effects similar to those associated with energy metabolism led us to explore whether neuroprotective effects of resveratrol are related to its role in autophagy regulation. We tested whether modulation of mammalian silent information regulator 2 (SIRT1) and/or metabolic energy sensor AMP-activated protein kinase (AMPK) are involved in autophagy induction by resveratrol, leading to neuronal survival. Our results showed that resveratrol protected against rotenone-induced apoptosis in SH-SY5Y cells and enhanced degradation of α-synucleins in α-synuclein-expressing PC12 cell lines via autophagy induction. We found that suppression of AMPK and/or SIRT1 caused decrease of protein level of LC3-II, indicating that AMPK and/or SIRT1 are required in resveratrol-mediated autophagy induction. Moreover, suppression of AMPK caused inhibition of SIRT1 activity and attenuated protective effects of resveratrol on rotenone-induced apoptosis, further suggesting that AMPK-SIRT1-autophagy pathway plays an important role in the neuroprotection by resveratrol on PD cellular models.
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