Abstract
Stroke is a common and serious nervous system disease caused by the rupture or blockage of the cardiovascular system. It causes millions of deaths and disabilities every year, which is a huge burden on humanity. It may be induced by thrombosis, hypertension, hyperlipidemia, hyperglycemia, smoking, advanced age and so on. According to different causes, stroke can be generally divided into hemorrhagic stroke and ischemic stroke, whose pathogenesis and treatment are quite different. Ferroptosis is a new type of cell death first defined in 2012, which is characterized by non-apoptotic, iron-dependent, and over-accumulated lipid peroxides. Excess lipid reactive oxygen species produced during ferroptosis eventually leads to oxidative cell death. Ferroptosis has been shown to occur and play an important role in tumors, neurological diseases, kidney injury, and ischemia–reperfusion injury. Ferroptosis is also closely related to the pathogenesis of stroke. Moreover, scientists have successfully intervened in the process of stroke in animal models by regulating ferroptosis, indicating that ferroptosis is a new potential target for the treatment of stroke. This paper systematically summarizes the involvement and role of ferroptosis in the pathogenesis of stroke and predicts the potential of ferroptosis in the treatment of stroke.
Graphical Abstract
Ferroptosis in stroke. Stroke induces iron overload and lipid metabolism disorders. Elevated iron catalyzes lipid peroxidation and eventually triggers ferroptosis. Conversely, the GSH/GPX4 pathway, as well as CoQ10, Fer-1, and Lip-1, inhibits lipid peroxidation and, thus, alleviates ferroptosis. GSH glutathione; GPX4 glutathione peroxidase 4; CoQ10 coenzyme Q10; Lip-1 liproxstatin-1; Fer-1 ferostatin-1.
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References
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This work was supported by the National Natural Science Foundation of China (No. 82172147, 81571880, 81373147, 30901555, 30972870, 81360080) and Natural Science Foundation of Hunan Province (2021JJ30900, 2016JJ2157), the Fundamental Research Funds for the Central Universities of Central South University (2020zzts222). All the funding bodies funded in the study design, collection, analysis, interpretation of data, and writing the manuscript.
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YL and JZ drafted, directed, and revised the review. YX, KL, LZ, and YZ collect reference articles. YX wrote the manuscript.
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Xu, Y., Li, K., Zhao, Y. et al. Role of Ferroptosis in Stroke. Cell Mol Neurobiol 43, 205–222 (2023). https://doi.org/10.1007/s10571-022-01196-6
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DOI: https://doi.org/10.1007/s10571-022-01196-6