Basic Research Paper
ER stress inhibits neuronal death by promoting autophagy
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Pages 915 - 926
http://dx.doi.org/10.4161/auto.19716
Keywords: Drosophila, ER stress, Parkinson, apoptosis, autophagy, mouse
Authors: Antoine Fouillet, Clemence Levet, Angelique Virgone, Marion Robin, Pierre Dourlen, Jennifer Rieusset, Elise Belaidi, Michel Ovize, Monique Touret, Serge Nataf and Bertrand Mollereau
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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.
Received: November 2, 2011; Accepted: February 15, 2012; Published Online: June 1, 2012
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