title: Resveratrol-activated AMPK/SIRT1/autophagy in cellular models of Parkinson's disease.
abstract: 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.
authors.affiliation: Department of Neurology, Shanghai First People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Yuncheng
authors.initials: Y
authors.lastname: Wu
authors.forename: Xinqun
authors.initials: X
authors.lastname: Li
authors.forename: Julie Xiaohong
authors.initials: JX
authors.lastname: Zhu
authors.forename: Wenjie
authors.initials: W
authors.lastname: Xie
authors.forename: Weidong
authors.initials: W
authors.lastname: Le
authors.forename: Zhen
authors.initials: Z
authors.lastname: Fan
authors.forename: Joseph
authors.initials: J
authors.lastname: Jankovic
authors.forename: Tianhong
authors.initials: T
authors.lastname: Pan
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D001343:Autophagy / Q000187:drug effects*; D002461:Cell Line, Transformed; D004305:Dose-Response Relationship, Drug; D004318:Doxycycline / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007306:Insecticides / Q000633:toxicity; D016253:Microscopy, Immunoelectron / Q000379:methods; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D051381:Rats; D000077185:Resveratrol; D012402:Rotenone / Q000633:toxicity; D015398:Signal Transduction / Q000187:drug effects*; D056564:Sirtuin 1 / Q000378:metabolism*; D013267:Stilbenes / Q000627:therapeutic use*; D013997:Time Factors; D051844:alpha-Synuclein / Q000235:genetics / Q000378:metabolism
chemical_list: D055372:AMP-Activated Protein Kinases; D000975:Antioxidants; D004318:Doxycycline; D007306:Insecticides; D008869:Microtubule-Associated Proteins; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D034741:RNA, Small Interfering; D000077185:Resveratrol; D012402:Rotenone; D056564:Sirtuin 1; D013267:Stilbenes; D051844:alpha-Synuclein; C526109:Anxa3 protein, rat; C499322:Parp1 protein, rat