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

Ferroptosis, a novel mode of programmed cell death, plays a significant role in neurological injury following ischemic stroke (IS). Nuclear factor E2-related factor 2 (Nrf2), a central transcription factor that combats oxidative stress, is a critical target for inhibiting ferroptosis by modulating iron metabolism, lipid peroxidation, and the glutathione system. In this paper, we systematically review the molecular mechanisms, signaling pathways, and potential therapeutic strategies, including pharmacological activators like dimethyl fumarate (DMF), natural compounds, and nanotechnology-based delivery systems, associated with the Nrf2 signaling pathway in the regulation of ferroptosis after cerebral ischemic injury. Additionally, we highlight future research directions, such as the development of targeted Nrf2 activators and investigations into cell-type-specific responses to ferroptosis modulation. This review underscores the therapeutic potential of Nrf2 signaling in IS while advocating for precision medicine approaches to address its dualistic challenges.