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We examined miRNA\u2013mRNA interactions in the gastrocnemius of hSOD1G93A mice across pre-, early- and late-symptomatic stages, using RNA sequencing, bioinformatics and reverse transcription quantitative PCR (RT-qPCR). Compared with hSOD1WT and non-transgenic control muscle, hSOD1G93A muscle showed mutation-specific transcriptome reprogramming: 48 dysregulated miRNAs and 558 mRNAs at pre-symptomatic, and 64 miRNAs and 685 mRNAs at late-symptomatic, stages. Functional enrichment pinpointed carbohydrate-handling pathways (glycolysis\/gluconeogenesis, pentose-phosphate, fructose\u2013mannose metabolism) as the dominant downregulated gene sets. Network analysis revealed clusters in which upregulated miRNAs converged on, and showed inverse expression patterns relative to metabolic transcripts. RT-qPCR confirmed inverse expression of ten candidate miRNAs and 11 metabolic mRNAs, substantiating miRNA-guided repression of glycolytic enzymes and energy-sensing nodes. Collectively, we show that SOD1G93A drives an early, sustained miRNA signature that dampens glycolysis gene expression, which could promote the fast-to-slow fibre-type transition and exacerbate energy deficit in ALS muscle. Targeting these circuits offers a strategy to restore metabolic balance and slow disease progression.<\/jats:p>","DOI":"10.1242\/dmm.052963","type":"journal-article","created":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T07:17:15Z","timestamp":1789024635000},"source":"Crossref","is-referenced-by-count":0,"title":["Dysregulated microRNA\u2013mRNA networks in SOD1G93A skeletal muscle reveal metabolic impairments in amyotrophic lateral sclerosis"],"prefix":"10.1242","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-3185-0330","authenticated-orcid":false,"given":"Libby","family":"Moody","sequence":"first","affiliation":[{"name":"School of Life Sciences, University of Sussex 1 Department of Neuroscience , , Brighton BN1 9QG ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9352-4908","authenticated-orcid":false,"given":"Eleni","family":"Christoforidou","sequence":"additional","affiliation":[{"name":"School of Life Sciences, University of Sussex 1 Department of Neuroscience , , Brighton BN1 9QG ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5827-6382","authenticated-orcid":false,"given":"Greig","family":"Joilin","sequence":"additional","affiliation":[{"name":"School of Life Sciences, University of Sussex 1 Department of Neuroscience , , Brighton BN1 9QG ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1409-2810","authenticated-orcid":false,"given":"Andrew","family":"Dilley","sequence":"additional","affiliation":[{"name":"Brighton and Sussex Medical School, University of Sussex 2 Department of Clinical Neuroscience , , Brighton BN1 9PX ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5262-7150","authenticated-orcid":false,"given":"Majid","family":"Hafezparast","sequence":"additional","affiliation":[{"name":"School of Life Sciences, University of Sussex 1 Department of Neuroscience , , Brighton BN1 9QG ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2026,10,9]]},"reference":[{"key":"2026100905400651500_DMM052963C1","doi-asserted-by":"publisher","first-page":"686","DOI":"10.1242\/dmm.007237","article-title":"A comprehensive assessment of the SOD1G93A low-copy transgenic mouse, which models human amyotrophic lateral sclerosis","volume":"4","author":"Acevedo-Arozena","year":"2011","journal-title":"Dis. 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