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Gene expression analysis of the spinal cord and gastrocnemius of the SOD1-G93A ALS mouse model revealed a strong increase in inflammatory pathways and, specifically in the ALS gastrocnemius, a decrease in mitochondrial transcription and an increase in ribosomal protein expression. Treatment of ALS mice with the polyamine spermidine (SPD), a promising molecule in combating neurodegeneration and muscle atrophy, is able to partially restore the expression of more than four thousand genes in gastrocnemius tissue, including the mitochondrial regulator Pgc1\u03b1, as well as all the mitochondrial encoded genes and a large class of ribosomal proteins. SPD enhanced mitochondrial bioenergetics, as evidenced by Seahorse experiments, and delayed muscle weakness in vivo, as shown by grip strength records. These findings suggest that SPD can act as a potential supplement in the therapeutic strategy for ALS, offering a foundation for further research to improve patient outcomes.<\/jats:p>","DOI":"10.3390\/biom16040566","type":"journal-article","created":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T12:01:52Z","timestamp":1775822512000},"page":"566","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Transcriptomic Analysis Reveals the Beneficial Effects of Spermidine in an ALS Mouse Model"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5804-3909","authenticated-orcid":false,"given":"Cristian","family":"Fiorucci","sequence":"first","affiliation":[{"name":"Department of Sciences, University of Roma Tre, 00146 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4485-7738","authenticated-orcid":false,"given":"Marianna","family":"Rossi","sequence":"additional","affiliation":[{"name":"Department of Sciences, University of Roma Tre, 00146 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-2002-3431","authenticated-orcid":false,"given":"Rachele","family":"Di Santo","sequence":"additional","affiliation":[{"name":"Department of Sciences, University of Roma Tre, 00146 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Illari","family":"Salvatori","sequence":"additional","affiliation":[{"name":"Laboratory of Neurochemistry IRCCS-Fondazione Santa Lucia, 00179 Rome, Italy"},{"name":"Institute of Translational Pharmacology (IFT), National Research Council (CNR), 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Scaricamazza","sequence":"additional","affiliation":[{"name":"Laboratory of Neurochemistry IRCCS-Fondazione Santa Lucia, 00179 Rome, Italy"},{"name":"Institute of Translational Pharmacology (IFT), National Research Council (CNR), 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-9905-7870","authenticated-orcid":false,"given":"Stefano","family":"Giuliani","sequence":"additional","affiliation":[{"name":"Department of Sciences, University of Roma Tre, 00146 Rome, Italy"},{"name":"Gene Expression and Cancer Models Unit, Department of Research and Advanced Technologies, Translational Research Area, IRCCS Regina Elena National Cancer Institute, 00144 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-8643-1401","authenticated-orcid":false,"given":"Olga","family":"Carletta","sequence":"additional","affiliation":[{"name":"Department of Sciences, University of Roma Tre, 00146 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-0914-8283","authenticated-orcid":false,"given":"Ermes","family":"Filomena","sequence":"additional","affiliation":[{"name":"Department of Biosciences, Biotechnology and Environment, University of Bari Aldo Moro, 70125 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-1148-5898","authenticated-orcid":false,"given":"Davide","family":"Laurenti","sequence":"additional","affiliation":[{"name":"Department of Biochemical Sciences \u201cA. 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