Résumé
Background: Amyotrophic lateral sclerosis (ALS) is a paralytic and fatal neurodegenerative disorder caused by the gradual loss of both upper and lower motoneurons. There is compelling evidence from ALS experimental models that neuroinflammation actively contributes to motoneuron damage. We recently proposed that interferon gamma (IFN?), a potent proinflammatory cytokine, induces motoneuron death by eliciting the activation of the lymphotoxin beta receptor (LT-beta R) through its ligand LIGHT. Here, we explore the pertinence of this non-cell-autonomous mechanism in human ALS.
Methods: The levels and expression pattern of IFN gamma, LIGHT, and LT-beta R were investigated by Western blot and immunohistochemical analysis in spinal cord of patients with sporadic ALS.
Results: We observed significant increased levels of IFN gamma in human ALS spinal cords compared to control cases. We found that large ventral horn neurons as well as glial cells were immunoreactive for IFN gamma in sporadic ALS spinal cord. We further observed that LIGHT and LT-beta R were expressed mainly by motoneurons in both ALS and control cases, and while LT-beta R levels remained constant between ALS and control cases, LIGHT levels were increased in human ALS spinal cords.
Conclusion: These findings in sporadic ALS cases, which are consistent with the observation made in ALS experimental models, propose that the IFN gamma-triggered LIGHT/LT-beta R-mediated death pathway may contribute to human ALS pathogenesis.