02INVBeyond muscular dystrophies: roles of MD-related proteins in different organ systems

Muscular dystrophies (MDs) are characterized by progressive muscle weakness and degeneration, caused by mutations in MD-related genes encoding proteins required for healthy muscle function. MD-related proteins are traditionally studied in the context of skeletal muscle, even though many are ubiquitously expressed, suggesting broader physiological roles. This presentation will first give an overview on the spectrum of additional organ involvements in MDs: while cardiac involvement is most frequently observed, MD-related proteins play crucial roles in various organ systems beyond muscle tissue, impacting nervous, ocular, vascular, respiratory, renal, hepatic, gastrointestinal, and metabolic functions, as well as various cellular processes. To address potential molecular mechanisms underlying the multi-organ manifestations of MDs, paradigmatic key proteins will be discussed in more detail. Exemplifying the clinical importance of exceeding skeletal muscle involvement, this presentation will then conclude on plectin, a multi-functional cytolinker and intermediate filament stabilizing protein essential for muscle fiber integrity and function. Mutations in the human plectin gene (PLEC) cause autosomal recessive epidermolysis bullosa simplex with muscular dystrophy (EBS-MD), which is characterized by skin blistering and progressive weakness, but also multiple additional symptoms. As evaluating disease-mimicking cell and animal models is inevitable for the understanding of the pathomechanistic basis of MDs and the development of treatment strategies, central results from corresponding molecular analyses will be highlighted as well. In conclusion, gaining a multi-systemic pathophysiological and molecular insight into MDs is inevitable for a comprehensive understanding and the development of therapeutic perspectives.