Fiche publication
Date publication
décembre 2008
Auteurs
Membres identifiés du Cancéropôle Est :
Dr LOEFFLER Jean-Philippe
Tous les auteurs :
Dupuis L, Loeffler JP
Lien Pubmed
Résumé
Amyotrophic lateral sclerosis (ALS) is the most frequent adult onset motor neuron disorder. A subset of ALS cases is linked to mutations in the copper/zinc superoxide dismutase (sod1) gene and detailed phenotypic analysis of transgenic mice overexpressing mutant forms of SOD1 (mSOD1) allowed a better understanding of the pathophysiological mechanisms leading to motor neuron death. The promising results obtained in these animal models however poorly translated into conclusive clinical trials. In this review, we summarize the main pathological mechanisms at work in mSOD1 mice. In particular, recent results showed that the key pathological event was the destruction of the neuromuscular junction rather than motor neuron death. Neuromuscular junction dismantlement is likely the result of a chronic energy deficiency at the level of the whole organism. These results, along with a comparative analysis between the phenotype of mSOD1 mice and ALS patients, suggest new therapeutic strategies and show the interests but also the limits of the animal models.
Référence
Med Sci (Paris). 2008 Dec;24(12):1077-82.