Wild-type huntingtin protects from apoptosis upstream of caspase-3

Dorotea Rigamonti, Johannes H. Bauer, Claudio De-Fraja, Luciano Conti, Simonetta Sipione, Clara Sciorati, Emilio Clementi, Abigail Hackam, Michael R. Hayden, Yong Li, Jillian K. Cooper, Christopher A. Ross, Stefano Govoni, Claudius Vincenz, Elena Cattaneo

Research output: Contribution to journalArticle

287 Scopus citations


Expansion of a polyglutamine sequence in the N terminus of huntingtin is the gain-of-function event that causes Huntington's disease. This mutation affects primarily the medium-size spiny neurons of the striatum. Huntingtin is expressed in many neuronal and non-neuronal cell types, implying a more general function for the wild-type protein. Here we report that wild-type huntingtin acts by protecting CNS cells from a variety of apoptotic stimuli, including serum withdrawal, death receptors, and pro-apoptotic Bcl-2 homologs. This protection may take place at the level of caspase-9 activation. The full-length protein also modulates the toxicity of the poly-Q expansion. Cells expressing full-length mutant protein are susceptible to fewer death stimuli than cells expressing truncated mutant huntingtin.

Original languageEnglish (US)
Pages (from-to)3705-3713
Number of pages9
JournalJournal of Neuroscience
Issue number10
StatePublished - May 15 2000


  • CAG
  • Caspases
  • CNS cells
  • Huntingtin
  • Huntington's disease
  • Survival

ASJC Scopus subject areas

  • Neuroscience(all)

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    Rigamonti, D., Bauer, J. H., De-Fraja, C., Conti, L., Sipione, S., Sciorati, C., Clementi, E., Hackam, A., Hayden, M. R., Li, Y., Cooper, J. K., Ross, C. A., Govoni, S., Vincenz, C., & Cattaneo, E. (2000). Wild-type huntingtin protects from apoptosis upstream of caspase-3. Journal of Neuroscience, 20(10), 3705-3713. https://doi.org/10.1523/jneurosci.20-10-03705.2000