The role of ferroptosis and its mechanism in ischemic stroke

Ischemic stroke is an acute cerebrovascular disease with a high morbidity, mortality, and disability rate. Persistent ischemia of brain tissue can cause irreversible damage to neurons, leading to neurological dysfunction and seriously affecting patients' quality of life. However, current clinical therapies are limited and have not achieved satisfactory outcome, due to the incomplete understanding of the mechanism of neuronal damage during ischemic stroke. Recent studies have found that ferroptosis is implicated in the pathophysiology of ischemic stroke. Ferroptosis is an iron-dependent regulated cell death driven by lipid peroxidation. Under normal physiological conditions, GSH/GPX4, FSP1/CoQ10, GCH/BH4 and other anti-ferroptosis pathways can function effectively to suppress the occurrence of ferroptosis. After ischemic stroke, two typical ferroptosis characteristics, lipid peroxidation and iron accumulation, are observed, accompanied by changes in the expression of ferroptosis related genes such as GPX4, ACSL4, and SLC7A11, suggesting that ferroptosis plays a key role in ischemic stroke, which provides a new idea for the clinical treatment of ischemic stroke. This article reviewed the pathological mechanisms of ferroptosis in the occurrence and development of ischemic stroke, as well as the related progress of ferroptosis targeted therapy.