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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


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


  1. 1

    Morley, J.F., Brignull, H.R., Weyers, J.J. & Morimoto, R.I. Proc. Natl. Acad. Sci. USA 99, 10417–10422 (2002).

    Article  Google Scholar 

  2. 2

    Ogg, S. et al. Nature 389, 994–999 (1997).

    CAS  Article  Google Scholar 

  3. 3

    Tissenbaum, H.A. & Guarente, L. Nature 410, 227–230 (2001).

    CAS  Article  Google Scholar 

  4. 4

    Wood, J.G. et al. Nature 430, 686–689 (2004).

    CAS  Article  Google Scholar 

  5. 5

    Brunet, A. et al. Science 303, 2011–2015 (2004).

    CAS  Article  Google Scholar 

  6. 6

    Motta, M.C. et al. Cell 116, 551–563 (2004).

    CAS  Article  Google Scholar 

  7. 7

    Howitz, K.T. et al. Nature 425, 191–196 (2003).

    CAS  Article  Google Scholar 

  8. 8

    Araki, T., Sasaki, Y. & Milbrandt, J. Science 305, 1010–1013 (2004).

    CAS  Article  Google Scholar 

  9. 9

    Rubinsztein, D.C. Trends Genet. 18, 202–209 (2002).

    CAS  Article  Google Scholar 

  10. 10

    Levine, M.S., Cepeda, C., Hickey, M.A., Fleming, S.M. & Chesselet, M.F. Trends Neurosci. 27, 691–697 (2004).

    CAS  Article  Google Scholar 

  11. 11

    Trettel, F. et al. Hum. Mol. Genet. 9, 2799–2809 (2000).

    CAS  Article  Google Scholar 

  12. 12

    Fulco, M. et al. Mol. Cell 12, 51–62 (2003).

    CAS  Article  Google Scholar 

  13. 13

    Murphy, C.T. et al. Nature 424, 277–283 (2003).

    CAS  Article  Google Scholar 

  14. 14

    Lee, S.S., Kennedy, S., Tolonen, A.C. & Ruvkun, G. Science 300, 644–647 (2003).

    CAS  Article  Google Scholar 

  15. 15

    Cohen, H.Y. et al. Science 305, 390–392 (2004).

    CAS  Article  Google Scholar 

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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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Parker, J., Arango, M., Abderrahmane, S. et al. Resveratrol rescues mutant polyglutamine cytotoxicity in nematode and mammalian neurons. Nat Genet 37, 349–350 (2005).

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