PD Dr. med Heike Kölbel (Essen / DE), Laximara Kollipara (Dortmund / DE), Dr. med. Adela Della Marina (Essen / DE), Prof. Dr. Matthias Vorgerd (Bochum / DE), Prof. Dr. med Ulrike Schara-Schmidt (Essen / DE), Prof. Dr. med Werner Stenzel (Berlin / DE), Prof. Tereshina Evangelista (Paris / FR), PD Dr.rer nat Andreas Roos (Essen / DE; Dortmund / DE; Bochum / DE; Ottawa, ON / CA)
Abstract-Text (inkl. Referenzen)
Aims:
Spinal muscular atrophy (SMA) is a neuromuscular disease characterized by significant reduction of SMN protein. This causes degeneration of lower motor neurons in the spinal cord and brainstem leading to weakness and muscle atrophy. Clinical severity is categorized in different subtypes (type 0-3), which is turn influenced by residual SMN level. While the genetic basis of SMA is well described, the tissue-specific molecular pathways underlying SMA are still not fully understood and identification of marker proteins in human vulnerable tissue such as skeletal muscle is still lacking.
Methods:
To elucidate molecular markers in SMA-diseased muscle, we performed unbiased proteomics and transcriptomics on muscle biopsies derived from 3 type 3 patients in addition to immunofluorescence including 5 additional cases.
Results:
Combined proteomic and transcriptomic studies unraveled FUS (a DNA/RNA-binding protein and aggregation marker) as a potential molecular marker increased in SMA muscle. Results of our immunofluorescence studies showed increased FUS protein abundance accompanied by perimyonuclear disposition of the protein in a proportion of myofibres compared to the immunoreactivity obtained in control samples.
Conclusion: Our data classified FUS as a protein involved in SMA-based myopathology and support the concept of skeletal muscle as a primary tissue target of SMA. Further studies are crucial to define the role of mis-localized FUS in SMA muscle.