01INVHow can proteomics help to elucidate the pathophysiological crosstalk in muscular dystrophy and associated multi-system dysfunction?

Mass spectrometry-based proteomics, based on both bottom-up or top-down biochemical approaches, represents a core analytical technique of systems biology that is deeply embedded in the multi-omics field of pathobiochemical research. This presentation focuses on the question of how large-scale proteomic surveys can be utilized to improve our understanding of the molecular and cellular mechanisms that underlie complex human disorders, such as Duchenne muscular dystrophy. Proteomic studies have confirmed that genetic abnormalities in the DMD gene severely affect the neuromuscular system and that loss of the cytoskeletal dystrophin protein isoform Dp427-M and concomitant reduction of its associated sarcolemmal glycoprotein complex triggers severe myofibre degeneration, chronic inflammation and reactive myofibrosis. Of note, dystrophinopathy is also characterized by multi-system pathophysiological alterations affecting especially the central nervous system, cardiorespiratory function, the kidneys and liver metabolism. Newly established proteomic biomarker signatures have the potential to enhance the comprehensive screening of these multi-system abnormalities, as well as improve differential diagnostics, prognostic evaluations, therapeutic monitoring, and the systematic identification of novel therapeutic targets to treat Duchenne muscular dystrophy. It is envisaged that the future integromic screening of muscular dystrophy would encompass the holistic integration of diverse omics-type methods, including tissue proteomics, single cell proteomics, subproteomics and biofluid proteomics.