title: [Amyotrophic lateral sclerosis: role of energy deficiency in neuromuscular junction dismantlement].
abstract: 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.
authors.affiliation: Inserm U692, Laboratoire SMN, Université Louis Pasteur, UMRS 692, Faculté de Médecine, 11, rue Humann, 67085 Strasbourg, France. ldupuis@neurochem.u-strasbg.fr
authors.forename: Luc
authors.initials: L
authors.lastname: Dupuis
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Loeffler
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000453:epidemiology / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001253:Astrocytes / Q000201:enzymology; D004195:Disease Models, Animal; D004734:Energy Metabolism; D006801:Humans; D008264:Macrophages / Q000201:enzymology; D051379:Mice; D008822:Mice, Transgenic; D008959:Models, Neurological; D009046:Motor Neurons / Q000201:enzymology; D032342:Muscle Cells / Q000201:enzymology; D009124:Muscle Proteins / Q000378:metabolism; D009185:Myelin Proteins / Q000172:deficiency / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009469:Neuromuscular Junction / Q000378:metabolism*; D000070798:Nogo Proteins; D010641:Phenotype; D013045:Species Specificity; D013482:Superoxide Dismutase / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D000072105:Superoxide Dismutase-1
chemical_list: D009124:Muscle Proteins; D009185:Myelin Proteins; D009419:Nerve Tissue Proteins; D000070798:Nogo Proteins; C000603199:RTN4 protein, human; C000603201:Rtn4 protein, mouse; C000606290:SOD1 protein, human; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1