Age-related dysfunctions of the autophagy lysosomal pathway in hippocampal pyramidal neurons under proteasome stress.
Neurobiol Aging
; 36(5): 1953-63, 2015 May.
Article
en En
| MEDLINE
| ID: mdl-25817083
Autophagy plays a key role in the maintenance of cellular homeostasis, and autophagy deregulation gives rise to severe disorders. Many of the signaling pathways regulating autophagy under stress conditions are still poorly understood. Using a model of proteasome stress in rat hippocampus, we have characterized the functional crosstalk between the ubiquitin proteasome system and the autophagy-lysosome pathway, identifying also age-related modifications in the crosstalk between both proteolytic systems. Under proteasome inhibition, both autophagy activation and resolution were efficiently induced in young but not in aged rats, leading to restoration of protein homeostasis only in young pyramidal neurons. Importantly, proteasome stress inhibited glycogen synthase kinase-3ß in young but activated in aged rats. This age-related difference could be because of a dysfunction in the signaling pathway of the insulin growth factor-1 under stress situations. Present data highlight the potential role of glycogen synthase kinase-3ß in the coordination of both proteolytic systems under stress situation, representing a key molecular target to sort out this deleterious effect.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Autofagia
/
Envejecimiento
/
Transducción de Señal
/
Células Piramidales
/
Glucógeno Sintasa Quinasa 3
/
Complejo de la Endopetidasa Proteasomal
/
Hipocampo
/
Lisosomas
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Neurobiol Aging
Año:
2015
Tipo del documento:
Article
País de afiliación:
España