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Caspase-8 is required for cell death induced by expanded polyglutamine repeats.

Authors: Sanchez, I  Xu, CJ  Juo, P  Kakizaka, A  Blenis, J  Yuan, J 
Citation: Sanchez I, etal., Neuron 1999 Mar;22(3):623-33.
Pubmed: (View Article at PubMed) PMID:10197541

We show here that caspase-8 is required for the death of primary rat neurons induced by an expanded polyglutamine repeat (Q79). Expression of Q79 recruited and activated caspase-8. Inhibition of caspase-8 blocked polyglutamine-induced cell death. Coexpression of Q79 with the caspase inhibitor CrmA, a dominant-negative mutant of FADD (FADD DN), Bcl-2, or Bcl-xL, but not an N-terminally tagged Bcl-xL, prevented the recruitment of caspase-8 and inhibited polyglutamine-induced cell death. Furthermore, Western blot analysis revealed the presence of activated caspase-8 in the insoluble fraction of affected brain regions from Huntington's disease (HD) patients but not in those from neurologically unremarkable controls, suggesting the relocation and activation of caspase-8 during the pathogenesis of HD. These results suggest an essential role of caspase-8 in HD-related neural degenerative diseases.

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RGD Object Information
RGD ID: 734695
Created: 2004-02-03
Species: All species
Last Modified: 2004-02-03
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.