Caspase-8 is required for cell death induced by expanded polyglutamine repeats.
Neuron
; 22(3): 623-33, 1999 Mar.
Article
en En
| MEDLINE
| ID: mdl-10197541
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.
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Banco de datos:
MEDLINE
Asunto principal:
Péptidos
/
Proteínas Virales
/
Apoptosis
/
Caspasas
/
Proteínas Adaptadoras Transductoras de Señales
/
Neuronas
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Neuron
Asunto de la revista:
NEUROLOGIA
Año:
1999
Tipo del documento:
Article
País de afiliación:
Estados Unidos