Resveratrol rescues mutant polyglutamine cytotoxicity in nematode and mammalian neurons.
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.
Parker
J Alex
JA
Institut National de la Santé et de la Recherche Médicale, Avenir Group, Laboratory of Genomic Biology, Centre Paul Broca, 75014 Paris, France.
Arango
Margarita
M
Abderrahmane
Salima
S
Lambert
Emmanuel
E
Tourette
Cendrine
C
Catoire
Hélène
H
Néri
Christian
C
D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D000818:Animals; D030801:Animals, Genetically Modified; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017173:Caenorhabditis elegans / Q000235:genetics / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D051858:Forkhead Transcription Factors; D006720:Homozygote; D008562:Membrane Glycoproteins / Q000235:genetics / Q000502:physiology*; D026901:Membrane Transport Proteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008817:Mice, Mutant Strains; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D010455:Peptides / Q000633:toxicity*; D000077185:Resveratrol; D050486:Serotonin Plasma Membrane Transport Proteins; D037761:Sirtuins / Q000235:genetics / Q000378:metabolism*; D013267:Stilbenes / Q000494:pharmacology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D020533:Angiogenesis Inhibitors; D000972:Antineoplastic Agents, Phytogenic; D029742:Caenorhabditis elegans Proteins; D051858:Forkhead Transcription Factors; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D010455:Peptides; D050486:Serotonin Plasma Membrane Transport Proteins; C493231:Slc6a4 protein, mouse; D013267:Stilbenes; D014157:Transcription Factors; C108831:daf-16 protein, C elegans; C097188:polyglutamine; D037761:Sirtuins; D000077185:Resveratrol