| Autor: |
Nastasia Cardone, Valentina Taglietti, Serena Baratto, Kaouthar Kefi, Baptiste Periou, Ciryl Gitiaux, Christine Barnerias, Peggy Lafuste, France Leturcq Pharm, Juliette Nectoux Pharm, Chiara Panicucci, Isabelle Desguerre, Claudio Bruno, François-Jerome Authier, Chiara Fiorillo, Frederic Relaix, Edoardo Malfatti |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
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| Zdroj: |
Acta Neuropathologica Communications, Vol 11, Iss 1, Pp 1-11 (2023) |
| Druh dokumentu: |
article |
| ISSN: |
2051-5960 |
| DOI: |
10.1186/s40478-023-01657-z |
| Popis: |
Abstract Duchenne muscular dystrophy (DMD) is a devastating X-linked muscular disease, caused by mutations in the DMD gene encoding Dystrophin and affecting 1:5000 boys worldwide. Lack of Dystrophin leads to progressive muscle wasting and degeneration resulting in cardiorespiratory failure. Despite the absence of a definitive cure, innovative therapeutic avenues are emerging. Myopathologic studies are important to further understand the biological mechanisms of the disease and to identify histopathologic benchmarks for clinical evaluations. We conducted a myopathologic analysis on twenty-four muscle biopsies from DMD patients, with particular emphasis on regeneration, fibro-adipogenic progenitors and muscle stem cells behavior. We describe an increase in content of fibro-adipogenic progenitors, central orchestrators of fibrotic progression and lipid deposition, concurrently with a decline in muscle regenerative capacity. This regenerative impairment strongly correlates with compromised activation and expansion of muscle stem cells. Furthermore, our study uncovers an early acquisition of a senescence phenotype by DMD-afflicted muscle stem cells. Here we describe the myopathologic trajectory intrinsic to DMD and establish muscle stem cell senescence as a pivotal readout for future therapeutic interventions. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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