{
  "abstract": "Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by the selective loss of dopaminergic neurons in the substantia nigra, leading to disabling motor and non-motor symptoms. Ferroptosis, an iron-dependent oxidative cell death driven by lethal lipid peroxidation, has emerged in preclinical models as a candidate pathogenic mechanism in PD, although its causal centrality in human PD remains to be established. Rotenone, a mitochondrial complex I inhibitor widely used to model PD, recapitulates key clinical and pathological features of the disease. Accumulating evidence demonstrates that rotenone induces ferroptosis through a coordinated network of iron dyshomeostasis, inactivation of the System Xc ⁻ –GPX4 antioxidant axis, dysregulated lipid metabolism, mitochondrial dysfunction, ferritinophagy-mediated iron release, neuroinflammation, and SIRT1–Nrf2 pathway suppression. Importantly, pharmacological targeting of these ferroptotic nodes—with agents such as Fer-1, iron chelators, Nrf2 activators, and modulators of ferritinophagy—effectively attenuates rotenone-induced neurodegeneration and restores motor function in preclinical models. This review systematically dissects the molecular circuitry of ferroptosis in rotenone -based PD models and evaluates the therapeutic potential of ferroptosis inhibitors, aiming to inform the development of disease-modifying strategies for PD.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Geriatrics, Aerospace Center Hospital, Peking University Aerospace School of Clinical Medicine",
    "Aerospace Medical Center, Aerospace Center Hospital",
    "GENERTEC Key Laboratory of Aerospace Medical Research and Transformation",
    "Department of Neurology, Hohhot First Hospital, Fifth Clinical Medical College, Inner Mongolia Medical University",
    "Department of Neurology, The Affiliated Hospital of Chifeng University",
    "Department of Neurology, Zhongnan Hospital of Wuhan University",
    "Hubei Provincial Clinical Research Center for Dementia and Cognitive Impairment"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Hongquan Wang"
    },
    {
      "affs": [
        3
      ],
      "name": "Zhiji Wang"
    },
    {
      "affs": [
        4
      ],
      "name": "Qiang Li"
    },
    {
      "affs": [
        5,
        6
      ],
      "name": "Shuang Wu"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Yumin Wang"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/9zwdym1wx6mn9.bib",
  "cited_by": 0,
  "doi": "10.3389/fphar.2026.1976646",
  "fulltext_url": null,
  "id": "9zwdym1wx6mn9",
  "issns": [
    "1663-9812"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fphar.2026.1976646/full",
  "language": null,
  "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": [
    [
      "openalex",
      "2728|Parkinson's Disease Mechanisms and Treatments"
    ]
  ],
  "openalex": "W7224095593",
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-28",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/9zwdym1wx6mn9.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:20:06Z",
      "native_id": "10.3389/fphar.2026.1976646",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fphar.2026.1976646/full"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2728|Parkinson's Disease Mechanisms and Treatments",
      "subfield": "neurology"
    }
  ],
  "title": "Targeting ferroptosis in rotenone-induced Parkinson’s disease: from mechanistic insights to pharmacological interventions",
  "title_text": "Targeting ferroptosis in rotenone-induced Parkinson’s disease: from mechanistic insights to pharmacological interventions",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:20:06Z",
  "url": "https://research.draconitic.com/paper/9zwdym1wx6mn9",
  "venue": "Frontiers in Pharmacology",
  "versions": []
}