title: Protective effects of resveratrol through the up-regulation of SIRT1 expression in the mutant hSOD1-G93A-bearing motor neuron-like cell culture model of amyotrophic lateral sclerosis.
abstract: Resveratrol has recently been widely reported to be an age-delaying and neuroprotective compound, and it appears to produce these benefits by activating silent mating type information regulation 2 homolog 1 (SIRT1). However, the role that SIRT1 activation plays in the pathogenesis of amyotrophic lateral sclerosis (ALS) remains unclear. In the present study, SIRT1 expression was found to be much lower in the mutant hSOD1G93A-bearing VSC4.1 cells compared to hSOD1wt cells when both were cultured in low-serum medium, indicating the involvement of SIRT1 activation defects in the pathogenesis of ALS under energetic stress. Further investigation revealed that a 24-h treatment with 0.5-20μM resveratrol had a dose-dependent protective effect on this ALS cell model, and the effects of resveratrol on increasing cell viability, preventing cell apoptosis and elevating cellular ATP levels through promoting mitochondria biogenesis were blocked by SIRT1 inhibition. This further demonstrated a role for SIRT1 activation in the protection of neuronal cells from degeneration. These findings suggest that resveratrol can protect the ALS cell model from mutant SOD1-mediated toxicity through up-regulating the expression of SIRT1, which represents a potential therapeutic target for preventing the motor neuron degeneration in ALS patients.
authors: Neurology Department of Peking University Third Hospital, 49 North Garden Road, Haidian District, Beijing 100191, China.
authors: Jing
authors: J
authors: Wang
authors: Yun
authors: Y
authors: Zhang
authors: Lu
authors: L
authors: Tang
authors: Nan
authors: N
authors: Zhang
authors: Dongsheng
authors: D
authors: Fan
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000473:pathology*; D017304:Annexin A5; D015153:Blotting, Western; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009046:Motor Neurons / Q000187:drug effects*; D009154:Mutation / Q000502:physiology; D018696:Neuroprotective Agents; D009536:Niacinamide / Q000494:pharmacology; D011419:Propidium; D060888:Real-Time Polymerase Chain Reaction; D000077185:Resveratrol; D056564:Sirtuin 1 / Q000096:biosynthesis* / Q000235:genetics; D013267:Stilbenes / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000235:genetics*; D000072105:Superoxide Dismutase-1; D013778:Tetrazolium Salts; D013844:Thiazoles; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D017304:Annexin A5; D018696:Neuroprotective Agents; C000606290:SOD1 protein, human; D013267:Stilbenes; D013778:Tetrazolium Salts; D013844:Thiazoles; D009536:Niacinamide; D011419:Propidium; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; C447939:SIRT1 protein, human; D056564:Sirtuin 1; C022616:thiazolyl blue; D000077185:Resveratrol