Resveratrol rescues mutant polyglutamine cytotoxicity in nematode and mammalian neurons

JA Parker, M Arango, S Abderrahmane, E Lambert… - Nature …, 2005 - nature.com
JA Parker, M Arango, S Abderrahmane, E Lambert, C Tourette, H Catoire, C Néri
Nature genetics, 2005nature.com
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.
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.
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