Manipulating Autophagy in Muscle Diseases

Autophagy is an evolutionary conserved cellular process involved in the clearance and recycling of various cell constituents, such as proteins, lipids, and exhausted organelles. Besides its importance in cell homeostasis and its contribution to cellular energy balance, autophagy is a fast and efficient response to different types of stress. For these reasons, mutation of autophagy genes and/or deregulation of the autophagic pathway are involved in a range of human disorders such as cancer, neurodegeneration, inflammation, and inherited muscle diseases. The interest in the role of autophagy in muscle came up when its role in maintaining muscle mass was discovered. Since then, several studies on animal models for different muscular dystrophies were performed by us and other groups, leading to the discovery that defective regulation of autophagy has a pathogenic role in the onset and progression of the muscle pathology. Even more important, our previous work demonstrated that modulation of autophagy, by either pharmacological means or specific dietary regimens aimed at restoring a proper autophagic flux, has beneficial effects and rescues the dystrophic phenotype. This collaborative project aims at studying the contribution of defective autophagy to the onset and progression of inherited muscle diseases and investigate the efficacy of different strategies aimed at restoring a normal autophagy in mouse models of muscular dystrophies, with the prospective aim of developing novel routes for therapy.