MUSCLE CONTROL OF MOTOR NEURON DEGENERATION AND SURVIVAL IN NEUROMUSCULAR DISEASES

The goal of our project is to define the factors that modulate muscle wasting associated with Amyotrophic Lateral Sclerosis (ALS). ALS is a member of a group of heterogeneous disorders that affect the survival and function of motor neurons, leading to muscle atrophy and paralysis. Although a significant proportion of familial ALS results from a toxic gain –of function associated with dominant SOD1 mutations, the etiology of the disease and its specific cellular origins have remained difficult to define. To date ALS is considered a motorneuron disease and treated as that, without a resolute treatment. In fact the only pharmacological drug approved is the glutamate antagonist Riluzole, although its effect is described as modest. We recently suggested that ALS is a multisystemic diseases where different tissues can be directly involved. In this project we propose to investigate the direct contribution of skeletal muscle to the pathogenesis of ALS disease, contributing to clarify the pathogenesis of ALS with the final goal to develop more appropriate therapeutic approaches.