ER stress inhibits neuronal death by promoting autophagy.
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.
Ecole Normale Supérieure de Lyon, Laboratoire de Biologie Moléculaire de la Cellule, Lyon, France.
Antoine
A
Fouillet
Clemence
C
Levet
Angelique
A
Virgone
Marion
M
Robin
Pierre
P
Dourlen
Jennifer
J
Rieusset
Elise
E
Belaidi
Michel
M
Ovize
Monique
M
Touret
Serge
S
Nataf
Bertrand
B
Mollereau
D000818:Animals; D001343:Autophagy / Q000187:drug effects; D019610:Cytoprotection / Q000187:drug effects; D004195:Disease Models, Animal; D004331:Drosophila melanogaster / Q000378:metabolism; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D051379:Mice; D009474:Neurons / Q000187:drug effects / Q000473:pathology*; D018696:Neuroprotective Agents / Q000494:pharmacology; D016627:Oxidopamine; D010300:Parkinson Disease / Q000473:pathology; D014415:Tunicamycin / Q000494:pharmacology
D018696:Neuroprotective Agents; D014415:Tunicamycin; D016627:Oxidopamine