NEW MECHANISMS FOR THE CONTROL OF TGF-BETA/MYOSTATIN SIGNALING IN MUSCULAR DYSTROPHY: MICRORNA, NEW EFFECTORS AND CROSSTALK WITH OTHER PATHWAYS

Understanding the mechanisms regulating the physiology and the formation of the skeletal muscle is crucial to define effective therapeutical approaches to cure myopathies, including muscular dystrophy. Of particular importance are therapies targeting signals that normally prevent muscular growth and that are required to maintain a reserve of undifferentiated muscle stem cells. Unfortunately these signals block - or unacceptably slow down - the regeneration of muscle subjected to repeated cycles of damage and repair, the typical condition of dystrophic patients. Here we propose to study one of the main pathway that inhibits muscle cells renewal, that is the signal triggered by Myostatin and related growth factors. More specifically, we propose to study two regulators of this cascade: a) a small non-coding RNA (microRNA) that blocks the Myostatin receptor; and b) an enzyme that inactivates one of the intracellular transducer of the pathway.