{
  "abstract": "Amyotrophic lateral sclerosis (ALS) is a multi-system disease in which skeletal muscle actively contributes to pathology, yet the regulatory circuits that drive muscle dysfunction remain unclear. We examined miRNA–mRNA 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–mannose 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.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Neuroscience, School of Life Sciences, University of Sussex, Brighton BN1 9QG, UK",
    "Department of Clinical Neuroscience, Brighton and Sussex Medical School, University of Sussex, Brighton BN1 9PX, UK"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Libby Moody",
      "orcid": "0009-0007-3185-0330"
    },
    {
      "affs": [
        0
      ],
      "name": "Eleni Christoforidou",
      "orcid": "0000-0002-9352-4908"
    },
    {
      "affs": [
        0
      ],
      "name": "Greig Joilin",
      "orcid": "0000-0001-5827-6382"
    },
    {
      "affs": [
        1
      ],
      "name": "Andrew Dilley",
      "orcid": "0000-0002-1409-2810"
    },
    {
      "affs": [
        0
      ],
      "name": "Majid Hafezparast",
      "orcid": "0000-0002-5262-7150"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/0rt0qe8d28h3x.bib",
  "cited_by": 0,
  "doi": "10.1242/dmm.052963",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13714871/",
  "id": "0rt0qe8d28h3x",
  "issns": [
    "1754-8403",
    "1754-8411"
  ],
  "landing_url": "https://doi.org/10.1242/dmm.052963",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Research Article"
    ],
    [
      "openalex",
      "2728|Amyotrophic Lateral Sclerosis Research"
    ]
  ],
  "openalex": "W7212149610",
  "pdf_url": null,
  "pmcid": "PMC13714871",
  "pmid": "42717683",
  "published": "2026-10-09",
  "publisher": "Company of Biologists",
  "ris": "https://research.draconitic.com/paper/0rt0qe8d28h3x.ris",
  "sources": [
    {
      "first_seen": "2026-11-01T12:22:17Z",
      "native_id": "PMC13714871",
      "source": "pmc",
      "url": "https://doi.org/10.1242/dmm.052963"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2728|Amyotrophic Lateral Sclerosis Research",
      "subfield": "neurology"
    }
  ],
  "title": "Dysregulated microRNA–mRNA networks in SOD1G93A skeletal muscle reveal metabolic impairments in amyotrophic lateral sclerosis",
  "title_text": "Dysregulated microRNA–mRNA networks in SOD1G93A skeletal muscle reveal metabolic impairments in amyotrophic lateral sclerosis",
  "type": "peer-reviewed",
  "updated_at": "2026-11-01T12:22:17Z",
  "url": "https://research.draconitic.com/paper/0rt0qe8d28h3x",
  "venue": "Disease Models & Mechanisms",
  "versions": []
}