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Resveratrol rescues mutant polyglutamine cytotoxicity in nematode and mammalian neurons

  • A Corrigendum to this article was published on 01 May 2005

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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Acknowledgements

This work was supported by the Institut National de la Santé et de la Recherche Médicale, the Cure Huntington's Disease Initiative of the High Q Foundation and the Association France Huntington. J.A.P. is supported by a postdoctoral fellowship from the Cure Huntington's Disease Initiative. M.A. is supported by a doctoral fellowship from the Institut National de la Santé et de la Recherche Médicale and the Région Ile-de-France. H.C. is supported by a doctoral fellowship from the Ministère de la Recherche.

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Correspondence to Christian Néri.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Fig. 1

Fisetin rescues mutant polyglutamine cytotoxicity. (PDF 1001 kb)

Supplementary Fig. 2

Increased sir-2.1 dosage protects axons from mutant polyglutamine-induced dystrophy. (PDF 865 kb)

Supplementary Fig. 3

Sirtuin inhibitors block resveratrol's rescue of mutant polyglutamine-induced cell death. (PDF 573 kb)

Supplementary Methods (PDF 140 kb)

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Figure 1: Rescue of mutant polyQ toxicity by increased sirtuin activity in nematode and mammalian neurons.