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Autophagy. 2012 Jun;8(6):915-26. doi: 10.4161/auto.19716. Epub 2012 Jun 1.

ER stress inhibits neuronal death by promoting autophagy.

Author information

1
Ecole Normale Supérieure de Lyon, Laboratoire de Biologie Moléculaire de la Cellule, Lyon, France.

Abstract

Endoplasmic reticulum (ER) stress has been implicated in neurodegenerative diseases but its relationship and role in disease progression remain unclear. Using genetic and pharmacological approaches, we showed that mild ER stress ("preconditioning") is neuroprotective in Drosophila and mouse models of Parkinson disease. In addition, we found that the combination of mild ER stress and apoptotic signals triggers an autophagic response both in vivo and in vitro. We showed that when autophagy is impaired, ER-mediated protection is lost. We further demonstrated that autophagy inhibits caspase activation and apoptosis. Based on our findings, we conclude that autophagy is required for the neuroprotection mediated by mild ER stress, and therefore ER preconditioning has potential therapeutic value for the treatment of neurodegenerative diseases.

PMID:
22660271
PMCID:
PMC3427257
DOI:
10.4161/auto.19716
[Indexed for MEDLINE]
Free PMC Article

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