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Growing evidence demonstrates that the pathological process leading to ALS is the result of multiple altered mechanisms occurring not only in MNs but also in other cell types inside and outside the central nervous system. In this context, the involvement of skeletal muscle has been the subject of a few studies on patients and ALS animal models. In this work, by using primary myocytes derived from the ALS transgenic hSOD1(G93A) mouse model, we observed that the myogenic capability of such cells was defective compared to cells derived from control mice expressing the nonpathogenic hSOD1(WT) isoform. The correct in vitro myogenesis of hSOD1(G93A) primary skeletal muscle cells was rescued by the addition of a conditioned medium from healthy hSOD1(WT) myocytes, suggesting the existence of an in trans activity of secreted factors. To define a dataset of molecules participating in such safeguard action, we conducted comparative metabolomic profiling of a culture medium collected from hSOD1(G93A) and hSOD1(WT) primary myocytes and report here an altered secretion of amino acids and lipid-based signaling molecules. These findings support the urgency of better understanding the role of the skeletal muscle secretome in the regulation of the myogenic program and mechanisms of ALS pathogenesis and progression.<\/jats:p>","DOI":"10.3390\/cells12232751","type":"journal-article","created":{"date-parts":[[2023,12,1]],"date-time":"2023-12-01T03:58:02Z","timestamp":1701403082000},"page":"2751","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Secreted Metabolome of ALS-Related hSOD1(G93A) Primary Cultures of Myocytes and Implications for Myogenesis"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1462-4423","authenticated-orcid":false,"given":"Roberto","family":"Stella","sequence":"first","affiliation":[{"name":"Istituto Zooprofilattico Sperimentale delle Venezie, 35020 Legnaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4832-2776","authenticated-orcid":false,"given":"Raphael Severino","family":"Bonadio","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Padova, 35131 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7271-4625","authenticated-orcid":false,"given":"Stefano","family":"Cagnin","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Padova, 35131 Padova, Italy"},{"name":"CIR-Myo Myology Center, University of Padova, 35131 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Andreotti","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of Padova, 35131 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1839-1404","authenticated-orcid":false,"given":"Maria Lina","family":"Massimino","sequence":"additional","affiliation":[{"name":"Neuroscience Institute, Consiglio Nazionale delle Ricerche, 35131 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1202-0191","authenticated-orcid":false,"given":"Alessandro","family":"Bertoli","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of Padova, 35131 Padova, Italy"},{"name":"Neuroscience Institute, Consiglio Nazionale delle Ricerche, 35131 Padova, Italy"},{"name":"Padova Neuroscience Center, University of Padova, 35131 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9967-2629","authenticated-orcid":false,"given":"Caterina","family":"Peggion","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Padova, 35131 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,11,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/j.neuron.2011.09.011","article-title":"Expanded GGGGCC Hexanucleotide Repeat in Noncoding Region of C9ORF72 Causes Chromosome 9p-Linked FTD and ALS","volume":"72","author":"Mackenzie","year":"2011","journal-title":"Neuron"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/j.neuron.2011.09.010","article-title":"A Hexanucleotide Repeat Expansion in C9ORF72 Is the Cause of Chromosome 9p21-Linked ALS-FTD","volume":"72","author":"Renton","year":"2011","journal-title":"Neuron"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1016\/S0896-6273(00)80272-X","article-title":"ALS-Linked SOD1 Mutant G85R Mediates Damage to Astrocytes and Promotes Rapidly Progressive Disease with SOD1-Containing Inclusions","volume":"18","author":"Bruijn","year":"1997","journal-title":"Neuron"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1038\/362059a0","article-title":"Mutations in Cu\/Zn Superoxide Dismutase Gene Are Associated with Familial Amyotrophic Lateral Sclerosis","volume":"362","author":"Rosen","year":"1993","journal-title":"Nature"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1772","DOI":"10.1126\/science.8209258","article-title":"Motor Neuron Degeneration in Mice That Express a Human Cu,Zn Superoxide Dismutase Mutation","volume":"264","author":"Gurney","year":"1994","journal-title":"Science"},{"key":"ref_6","first-page":"1271","article-title":"Development of Central Nervous System Pathology in a Murine Transgenic Model of Human Amyotrophic Lateral Sclerosis","volume":"145","author":"Gurney","year":"1994","journal-title":"Am. 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