Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
, 36 (5), 1953-63

Age-related Dysfunctions of the Autophagy Lysosomal Pathway in Hippocampal Pyramidal Neurons Under Proteasome Stress

Affiliations

Age-related Dysfunctions of the Autophagy Lysosomal Pathway in Hippocampal Pyramidal Neurons Under Proteasome Stress

Elena Gavilán et al. Neurobiol Aging.

Abstract

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-3β 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-3β in the coordination of both proteolytic systems under stress situation, representing a key molecular target to sort out this deleterious effect.

Keywords: Aging; Autophagy; GSK-3β; Hippocampus; Neurodegeneration.

Similar articles

See all similar articles

Cited by 10 PubMed Central articles

See all "Cited by" articles

Publication types

MeSH terms

LinkOut - more resources

Feedback