Abstract
In the present study, we investigated whether resveratrol, a SIRT1 activator, can suppress the motor neuron degeneration in a transgenic mouse model of amyotrophic lateral sclerosis. Chronic intraperitoneal injection of resveratrol delayed the disease onset and extended survival of the transgenic mice overexpressing G93A-SOD1. The number of surviving motor neurons increased in the resveratrol-injected G93A mice. Importantly, the levels of Hsp25 and Hsp70 were elevated while the level of heat shock factor 1 (HSF1) acetylation decreased in the spinal cords of the resveratrol-injected G93A mice. Our data suggest that resveratrol may protect motor neurons from the mutant SOD1-induced neurotoxicity by promoting SIRT1-mediated deacetylation of HSF1 and subsequent upregulation of Hsps.
Copyright © 2012 Elsevier B.V. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amyotrophic Lateral Sclerosis / drug therapy*
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Amyotrophic Lateral Sclerosis / genetics
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Amyotrophic Lateral Sclerosis / mortality*
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Animals
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Antioxidants / therapeutic use*
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DNA-Binding Proteins / metabolism
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Disease Models, Animal
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Glial Fibrillary Acidic Protein / metabolism
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HSP70 Heat-Shock Proteins / genetics
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HSP70 Heat-Shock Proteins / metabolism
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Heat Shock Transcription Factors
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Heat-Shock Proteins / metabolism*
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Humans
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Macrophage-1 Antigen / metabolism
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Mice
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Mice, Inbred C57BL
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Mice, Transgenic
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Molecular Chaperones
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Motor Neurons / drug effects
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Neoplasm Proteins / metabolism
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Resveratrol
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Spinal Cord / pathology
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Stilbenes / therapeutic use*
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Superoxide Dismutase / genetics
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Survival Analysis
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Transcription Factors / metabolism
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Up-Regulation / drug effects*
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Up-Regulation / genetics
Substances
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Antioxidants
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DNA-Binding Proteins
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Glial Fibrillary Acidic Protein
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HSP70 Heat-Shock Proteins
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Heat Shock Transcription Factors
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Heat-Shock Proteins
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Hsbp1 protein, mouse
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Hsf1 protein, mouse
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Macrophage-1 Antigen
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Molecular Chaperones
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Neoplasm Proteins
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Stilbenes
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Transcription Factors
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SOD1 G93A protein
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Superoxide Dismutase
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Resveratrol