An update on the role of ferroptosis in ischemic stroke: from molecular pathways to Neuroprotection.

Introduction: Ischemic stroke (IS), a major cause of mortality and disability worldwide, remains a significant healthcare challenge due to limited therapeutic options. Ferroptosis, a distinct iron-dependent form of regulated cell death characterized by lipid peroxidation and oxidative stress, has emerged as a crucial mechanism in IS pathophysiology. This review explores the role of ferroptosis in IS and its potential for driving innovative therapeutic strategies.

Area covered: This review delves into the practical implications of ferroptosis in IS, focusing on molecular mechanisms like lipid peroxidation, iron accumulation, and their interplay with inflammation, reactive oxygen species (ROS), and the Nrf2-ARE antioxidant system. It highlights ferroptotic proteins, small-molecule inhibitors, and non-coding RNA modulators as emerging therapeutic targets to mitigate neuroinflammation and neuronal cell death. Studies from PubMed (1982-2024) were identified using MeSH terms such as 'Ferroptosis' and 'Ischemic Stroke,' and only rigorously screened articles were included.

Expert opinion: Despite preclinical evidence supporting the neuroprotective effects of ferroptosis inhibitors, clinical translation faces hurdles such as suboptimal pharmacokinetics and safety concerns. Advances in drug delivery systems, bioinformatics, and AI-driven drug discovery may optimize ferroptosis-targeting strategies, develop biomarkers, and improve therapeutic outcomes for IS patients.