Caspase-8 is required for cell death induced by expanded polyglutamine repeats
- PMID: 10197541
- DOI: 10.1016/s0896-6273(00)80716-3
Caspase-8 is required for cell death induced by expanded polyglutamine repeats
Abstract
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.
Comment in
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Harm's way: polyglutamine repeats and the activation of an apoptotic pathway.Neuron. 1999 Mar;22(3):416-7. doi: 10.1016/s0896-6273(00)80695-9. Neuron. 1999. PMID: 10197520 No abstract available.
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