Understanding the role of CNBP-eIF5A-polyamine metabolism in DM2 pathogenesis

Myotonic Dystrophy 2 (DM2) is a genetic disease primarily affecting skeletal muscle, caused by a mutation of the CNBP/ZNF9 gene. To date the molecular mechanisms underlying DM2 are not understood, and a resolutive therapy is currently missing. In a previous study we have discovered that reduction of the CNBP gene product in the muscle affects locomotor function by causing a decrease of polyamines, small molecules that are critical for muscle cell survival. In this proposal we aim at elucidating whether reduced polyamines cause impairment of muscle function by affecting autophagy, a process that protects muscle cells when nutrients are low or unavailable. Results from this work might open the door to novel therapeutic strategies for a disease that still lacks a cure.