Heat shock response activation exacerbates inclusion body formation in a cellular model of Huntington disease.
J Biol Chem
; 288(33): 23633-8, 2013 Aug 16.
Article
en En
| MEDLINE
| ID: mdl-23839939
ABSTRACT
The cellular heat shock response (HSR) protects cells from toxicity associated with defective protein folding, and this pathway is widely viewed as a potential pharmacological target to treat neurodegenerative diseases linked to protein aggregation. Here we show that the HSR is not activated by mutant huntingtin (HTT) even in cells selected for the highest expression levels and for the presence of inclusion bodies containing aggregated protein. Surprisingly, HSR activation by HSF1 overexpression or by administration of a small molecule activator lowers the concentration threshold at which HTT forms inclusion bodies in cells expressing aggregation-prone, polyglutamine-expanded fragments of HTT. These data suggest that the HSR does not mitigate inclusion body formation.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Cuerpos de Inclusión
/
Enfermedad de Huntington
/
Respuesta al Choque Térmico
/
Modelos Biológicos
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
J Biol Chem
Año:
2013
Tipo del documento:
Article
País de afiliación:
Estados Unidos