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Mice carrying the SOD1G93A transgene with different genetic backgrounds show variable disease rates, reflecting the diversity of patients. While extensive research has been done on the involvement of the central nervous system, the role of skeletal muscle remains underexplored. We examined the impact of angiogenin, including its RNase activity, in skeletal muscles of ALS mouse models and in biopsies from ALS patients. Elevated levels of angiogenin were found in slowly progressing mice but not in rapidly progressing mice, correlating with increased muscle regeneration and vascularisation. In patients, higher levels of angiogenin in skeletal muscles correlated with milder disease. Mechanistically, angiogenin promotes muscle regeneration and vascularisation through satellite cell\u2010endothelial interactions during myogenesis and angiogenesis. Furthermore, specific angiogenin\u2010derived tiRNAs were upregulated in slowly progressing mice, suggesting their role in mediating the effects of angiogenin. These findings highlight angiogenin and its tiRNAs as potential prognostic markers and therapeutic targets for ALS, offering avenues for patient stratification and interventions to mitigate disease progression by promoting muscle regeneration.<\/jats:p>","DOI":"10.1111\/bpa.13328","type":"journal-article","created":{"date-parts":[[2024,12,28]],"date-time":"2024-12-28T05:03:06Z","timestamp":1735362186000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Protective role of Angiogenin in muscle regeneration in amyotrophic lateral sclerosis: Diagnostic and therapeutic implications"],"prefix":"10.1111","volume":"35","author":[{"given":"Paola","family":"Fabbrizio","sequence":"first","affiliation":[{"name":"Laboratory of Neurobiology and Molecular Therapeutics, Department of Neuroscience Istituto di Ricerche Farmacologiche Mario Negri IRCCS  Milano Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sharada","family":"Baindoor","sequence":"additional","affiliation":[{"name":"Department of Physiology and Medical Physics and SFI FutureNeuro Centre Royal College of Surgeons in Ireland  Dublin Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cassandra","family":"Margotta","sequence":"additional","affiliation":[{"name":"Laboratory of Neurobiology and Molecular Therapeutics, Department of Neuroscience Istituto di Ricerche Farmacologiche Mario Negri IRCCS  Milano Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junyi","family":"Su","sequence":"additional","affiliation":[{"name":"Omiics ApS  Aarhus Denmark"},{"name":"Interdisciplinary Nanoscience Center (iNANO) and Department of Molecular Biology and Genetics Aarhus University  Aarhus Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena P.","family":"Morrissey","sequence":"additional","affiliation":[{"name":"Department of Physiology and Medical Physics and SFI FutureNeuro Centre Royal College of Surgeons in Ireland  Dublin Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ina","family":"Woods","sequence":"additional","affiliation":[{"name":"Department of Physiology and Medical Physics and SFI FutureNeuro Centre Royal College of Surgeons in Ireland  Dublin Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marion C.","family":"Hogg","sequence":"additional","affiliation":[{"name":"Department of Physiology and Medical Physics and SFI FutureNeuro Centre Royal College of Surgeons in Ireland  Dublin Ireland"},{"name":"School of Science and Technology Nottingham Trent University  UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara","family":"Vianello","sequence":"additional","affiliation":[{"name":"Department of Neuroscience Azienda Ospedaliera di Padova  Padua Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Morten T.","family":"Ven\u00f8","sequence":"additional","affiliation":[{"name":"Omiics ApS  Aarhus Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J\u00f8rgen","family":"Kjems","sequence":"additional","affiliation":[{"name":"Interdisciplinary Nanoscience Center (iNANO) and Department of Molecular Biology and Genetics Aarhus University  Aarhus Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gianni","family":"Sorar\u00f9","sequence":"additional","affiliation":[{"name":"Department of Neuroscience Azienda Ospedaliera di Padova  Padua Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1055-1271","authenticated-orcid":false,"given":"Caterina","family":"Bendotti","sequence":"additional","affiliation":[{"name":"Laboratory of Neurobiology and Molecular Therapeutics, Department of Neuroscience Istituto di Ricerche Farmacologiche Mario Negri IRCCS  Milano Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3479-7794","authenticated-orcid":false,"given":"Jochen H. 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