Iron Dysregulation as Convergent Pathomechanism

Proposed by etl-backfill

GPX4 neuroinflammation market 52% active
Compare across mechanisms →
Composite
46%
Novelty
50%
Feasibility
50%
Impact
—
Mechanistic
50%
Druggability
50%
Safety
50%
Confidence
50%

Mechanistic description

Multiple myelopathy etiologies converge through disruption of spinal cord iron homeostasis, leading to ferroptosis-mediated cell death and standardized patterns of tissue damage.

Mechanism / pathway

  1. GPX4
  2. neuroinflammation

Evidence for (5)

  • Palmitoylation-dependent regulation of GPX4 suppresses ferroptosis.

    PMID:39833225 2025 Nat Commun

  • DHODH-mediated ferroptosis defence is a targetable vulnerability in cancer.

    PMID:33981038 2021 Nature

  • Palmitoylation of GPX4 via the targetable ZDHHC8 determines ferroptosis sensitivity and antitumor immunity.

    PMID:40108413 2025 Nat Cancer

  • STING aggravates ferroptosis-dependent myocardial ischemia-reperfusion injury by targeting GPX4 for autophagic degradation.

    PMID:40274801 2025 Signal Transduct Target Ther

  • GPX4 in cell death, autophagy, and disease.

    PMID:37272058 2023 Autophagy

Evidence against (3)

  • The essential elements of Alzheimer's disease.

    PMID:33219130 2021 J Biol Chem

  • GPX4 in cell death, autophagy, and disease.

    PMID:37272058 2023 Autophagy

  • Molecular mechanisms of ferroptosis and their involvement in brain diseases.

    PMID:36894028 2023 Pharmacol Ther

Evidence matrix

5 supporting 3 contradicting
63% supporting

Supporting

  • Palmitoylation-dependent regulation of GPX4 suppresses ferroptosis. PMID:39833225 · 2025 · Nat Commun
  • DHODH-mediated ferroptosis defence is a targetable vulnerability in cancer. PMID:33981038 · 2021 · Nature
  • Palmitoylation of GPX4 via the targetable ZDHHC8 determines ferroptosis sensitivity and antitumor immunity. PMID:40108413 · 2025 · Nat Cancer
  • STING aggravates ferroptosis-dependent myocardial ischemia-reperfusion injury by targeting GPX4 for autophagic degradation. PMID:40274801 · 2025 · Signal Transduct Target Ther
  • GPX4 in cell death, autophagy, and disease. PMID:37272058 · 2023 · Autophagy

Contradicting

  • The essential elements of Alzheimer's disease. PMID:33219130 · 2021 · J Biol Chem
  • GPX4 in cell death, autophagy, and disease. PMID:37272058 · 2023 · Autophagy
  • Molecular mechanisms of ferroptosis and their involvement in brain diseases. PMID:36894028 · 2023 · Pharmacol Ther

Cite this hypothesis

Cite this hypothesis
Citation

etl-backfill (2026). Iron Dysregulation as Convergent Pathomechanism. SciDEX hypothesis. https://prism.scidex.ai/hypotheses/hyp-SDA-2026-04-08-gap-pubmed-20260406-062111-db808ee9-6

BibTeX 
@misc{scidex_hypothesis_hypsda20,
  title        = {Iron Dysregulation as Convergent Pathomechanism},
  author       = {etl-backfill},
  year         = {2026},
  howpublished = {SciDEX hypothesis},
  url          = {https://prism.scidex.ai/hypotheses/hyp-SDA-2026-04-08-gap-pubmed-20260406-062111-db808ee9-6},
  note         = {SciDEX artifact hypothesis:hyp-SDA-2026-04-08-gap-pubmed-20260406-062111-db808ee9-6}
}

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