TY - JOUR AU - Fernández-Simón, Esther AU - Lleixà, Cinta AU - Suarez-Calvet, Xavier AU - Diaz-Manera, Jordi AU - Illa, Isabel AU - Gallardo, Eduard AU - de Luna, Noemí PY - 2020 DA - 2020/11/27 TI - Proteasome inhibitors reduce thrombospondin-1 release in human dysferlin-deficient myotubes JO - BMC Musculoskeletal Disorders SP - 784 VL - 21 IS - 1 AB - Dysferlinopathies are a group of muscle disorders causing muscle weakness and absence or low levels of dysferlin, a type-II transmembrane protein and the causative gene of these dystrophies. Dysferlin is implicated in vesicle fusion, trafficking, and membrane repair. Muscle biopsy of patients with dysferlinopathy is characterized by the presence of inflammatory infiltrates. Studies in the muscle of both human and mouse models of dysferlinopathy suggest dysferlin deficient muscle plays a role in this inflammation by releasing thrombospondin-1. It has also been reported that vitamin D3 treatment enhances dysferlin expression. The ubiquitin-proteasome system recognizes and removes proteins that fail to fold or assemble properly and previous studies suggest that its inhibition could have a therapeutic effect in muscle dystrophies. Here we assessed whether inhibition of the ubiquitin proteasome system prevented degradation of dysferlin in immortalized myoblasts from a patients with two missense mutations in exon 44. SN - 1471-2474 UR - https://doi.org/10.1186/s12891-020-03756-7 DO - 10.1186/s12891-020-03756-7 ID - Fernández-Simón2020 ER -