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.
© 2011 S. Karger AG, Basel
- Parkinson’s disease
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Dr. Tianhong Pan
Parkinson Disease Research Laboratory
Department of Neurology, Baylor College of Medicine
One Baylor Plaza, MS NB302, Houston, TX 77030 (USA)
Tel. +1 713 798 5142, E-Mail firstname.lastname@example.org
Received: January 4, 2011
Accepted after revision: April 18, 2011
Published online: July 22, 2011
Number of Print Pages : 12
Number of Figures : 7, Number of Tables : 0, Number of References : 64
Vol. 19, No. 3, Year 2011 (Cover Date: August 2011)
Journal Editor: Ip N.Y. (Hong Kong)
ISSN: 1424-862X (Print), eISSN: 1424-8638 (Online)
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