Résumé :
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Muscular dystrophies (MD) are a group of genetic diseases characterized by progressive muscle degeneration and weakness. Muscle atrophy is a very common clinical feature of these pathologies. In an attempt to identify potential therapeutic targets for the correction of muscle wasting in muscular dystrophies, the expression of several pivotal proteins involved in protein metabolism was investigated in 4 MD animal models (deficient for calpain 3, ?-sarcoglycan, dystrophin and dysferlin respectively) as well as experimental atrophy induced by transient or definitive denervation. Amongst all the proteins considered: i) FoxO1 expression is increased in every muscle of a LGMD2A murine model and ii) the expression of CARP, a regulator of transcription factors, appears to be the only one systematically rising in all MD models. CARP is also persistently up-regulated in atrophy-induced denervation, whereas MAFbx and MURF1, two E3 ubiquitin ligases known to be involved in muscle wasting, are only transiently over-expressed. CARP over-expression in muscle fibres fails to induce atrophy, indicating that CARP per se cannot initiate the phenomenon. Finally, we propose the down-regulation of these 2 major markers as potential therapeutic strategies: FoxO1 in LGMD2A and CARP in muscular pathologies.
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