Insight into Crosstalk between Ferroptosis and Necroptosis: Novel Therapeutics in Ischemic Stroke

Figure 1

The mechanisms of ferroptosis in ischemic stroke. (1) Following ischemic stroke, BBB is disrupted, which allows Fe (III) in the blood to be released into the brain parenchyma with the cooperation of TF and TFR1. Fe (III) is transported from the endosome to the cytoplasm as Fe (II) by DMT1 with the cooperation of STEAP3. Iron overload accelerates lipid ROS accumulation and ferroptosis via Fenton reaction. (2) System x_c- is simultaneously impaired, which inhibits cystine-glutamate exchange and decreases the generation of the antioxidant GSH and GPX4. (3) Metabolic imbalances of lipids and amino acids aggravate lipid ROS accumulation and ferroptosis. LPCAT3: lysophosphatidylcholine acyltransferase 3; H₂O₂: hydrogen peroxide; GSSG: oxidized glutathione.