Article Dans Une Revue Cell Death and Differentiation Année : 2010

IFNγ triggers a LIGHT-dependent selective death of motoneurons contributing to the non-cell-autonomous effects of mutant SOD1

Résumé

Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disease that primarily affects motoneurons in the brain and spinal cord. Dominant mutations in superoxide dismutase-1 (SOD1) cause a familial form of amyotrophic lateral sclerosis (ALS). Mutant SOD1 damaged glial cells contribute to ALS pathogenesis by releasing neurotoxic factors, but the mechanistic basis of the motoneuron-specific elimination is poorly understood. Here, we describe a motoneuron selective death pathway triggered by activation of LT-βR by LIGHT, and operating by a novel signaling scheme. We show that astrocytes expressing mutant SOD1 mediate the selective death of motoneurons through the proinflammatory cytokine interferon-gamma (IFNγ), which activates the LIGHT-LT-βR death pathway. The expression of LIGHT and LT-βR by motoneurons in vivo correlates with the preferential expression of IFNγ by motoneurons and astrocytes at disease onset and symptomatic stage in ALS mice. Importantly, the genetic ablation of Light in an ALS mouse model retards progression, but not onset, of the disease and increases lifespan. We propose that IFNγ contributes to a cross-talk between motoneurons and astrocytes causing the selective loss of some motoneurons following activation of the LIGHT-induced death pathway.

Fichier principal
Vignette du fichier
PEER_stage2_10.1038%2Fcdd.2010.143.pdf (833.71 Ko) Télécharger le fichier
Origine Fichiers produits par l'(les) auteur(s)
Licence
Loading...

Dates et versions

hal-00592289 , version 1 (12-05-2011)

Licence

Identifiants

Citer

Cedric Raoul, Julianne Aebischer, Patricia Cassina, Belkacem Otsmane, Anice Moumen, et al.. IFNγ triggers a LIGHT-dependent selective death of motoneurons contributing to the non-cell-autonomous effects of mutant SOD1. Cell Death and Differentiation, 2010, ⟨10.1038/cdd.2010.143⟩. ⟨hal-00592289⟩

Collections

142 Consultations
147 Téléchargements

Altmetric

Partager

  • More