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Pathogenesis and role of ferroptosis mediated by Nrf2 signaling pathway in ischemic stroke

Nitong Ying1, Yongyan Wang1, Zirong Li1

  • 1Department of Human Anatomy, Medical School, Kunming University of Science and Technology, Kunming, 650500, PR China.

Biochemical and Biophysical Research Communications
|July 31, 2026
PubMed

Insights

Nuclear factor E2-related factor 2 (Nrf2) signaling regulates ferroptosis, a cell death form impacting ischemic stroke (IS) neurological injury. Targeting Nrf2 offers therapeutic potential for IS by modulating oxidative stress and cell death pathways.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Biochemistry

Background:

  • Ferroptosis is a programmed cell death form implicated in neurological damage after ischemic stroke (IS).
  • Nuclear factor E2-related factor 2 (Nrf2) is a key regulator of cellular responses to oxidative stress.
  • Nrf2 influences iron metabolism, lipid peroxidation, and glutathione pathways, all relevant to ferroptosis.

Purpose of the Study:

  • To systematically review the molecular mechanisms and signaling pathways of Nrf2 in regulating ferroptosis post-cerebral ischemic injury.
  • To explore potential therapeutic strategies targeting the Nrf2 pathway for IS treatment.
  • To identify future research directions in Nrf2-mediated ferroptosis modulation.

Main Methods:

  • Systematic literature review focusing on Nrf2 signaling, ferroptosis, and cerebral ischemia.
  • Analysis of molecular mechanisms, signaling pathways, and therapeutic interventions.
  • Identification of research gaps and future prospects.

Main Results:

  • Nrf2 is a critical target for inhibiting ferroptosis by modulating key metabolic pathways.
  • Pharmacological activators (e.g., dimethyl fumarate), natural compounds, and nanotechnology show promise in Nrf2-based therapies.
  • Nrf2 signaling presents therapeutic potential but requires precision medicine approaches due to its complexity.

Conclusions:

  • The Nrf2 signaling pathway is a significant regulator of ferroptosis in the context of ischemic stroke.
  • Targeting Nrf2 offers a promising therapeutic avenue for mitigating neurological injury.
  • Further research into targeted Nrf2 activators and cell-type-specific responses is warranted for effective clinical translation.
Keywords:
FerroptosisIron metabolismIschemic strokeNeuroprotectionNrf2Oxidative stress

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