Abstract
We report that Sir2 activation through increased sir-2.1 dosage or treatment with the sirtuin activator resveratrol specifically rescued early neuronal dysfunction phenotypes induced by mutant polyglutamines in transgenic Caenorhabditis elegans. These effects are dependent on daf-16 (Forkhead). Additionally, resveratrol rescued mutant polyglutamine-specific cell death in neuronal cells derived from HdhQ111 knock-in mice. We conclude that Sir2 activation may protect against mutant polyglutamines.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Angiogenesis Inhibitors / pharmacology
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Animals
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Animals, Genetically Modified
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Antineoplastic Agents, Phytogenic / pharmacology*
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Caenorhabditis elegans / genetics
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Caenorhabditis elegans / physiology*
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Caenorhabditis elegans Proteins / genetics
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Caenorhabditis elegans Proteins / metabolism*
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Forkhead Transcription Factors
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Homozygote
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Membrane Glycoproteins / genetics
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Membrane Glycoproteins / physiology*
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Membrane Transport Proteins / genetics
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Membrane Transport Proteins / physiology*
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Mice
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Mice, Mutant Strains
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / physiology*
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Neurons / cytology
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Neurons / physiology*
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Peptides / toxicity*
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Resveratrol
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Serotonin Plasma Membrane Transport Proteins
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Sirtuins / genetics
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Sirtuins / metabolism*
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Stilbenes / pharmacology*
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Transcription Factors / genetics
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Transcription Factors / metabolism*
Substances
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Angiogenesis Inhibitors
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Antineoplastic Agents, Phytogenic
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Caenorhabditis elegans Proteins
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Forkhead Transcription Factors
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Membrane Glycoproteins
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Membrane Transport Proteins
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Nerve Tissue Proteins
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Peptides
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Serotonin Plasma Membrane Transport Proteins
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Slc6a4 protein, mouse
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Stilbenes
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Transcription Factors
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daf-16 protein, C elegans
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polyglutamine
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Sirtuins
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Resveratrol