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Review
. 2021 Jan-Dec:13:17590914211037505.
doi: 10.1177/17590914211037505.

Emerging Role of Ferroptosis in the Pathogenesis of Ischemic Stroke: A New Therapeutic Target?

Zhong-Qi Bu  1 , Hai-Yang Yu  1 , Jue Wang  1 , Xin He  1 , Yue-Ran Cui  1 , Jia-Chun Feng  2 , Juan Feng  1
Affiliations
Review

Emerging Role of Ferroptosis in the Pathogenesis of Ischemic Stroke: A New Therapeutic Target?

Zhong-Qi Bu et al. ASN Neuro. 2021 Jan-Dec.

Abstract

Ischemic stroke is one of the main causes of high morbidity, mortality, and disability worldwide; however, the treatment methods are limited and do not always achieve satisfactory results. The pathogenesis of ischemic stroke is complex, defined by multiple mechanisms; among them, programmed death of neuronal cells plays a significant role. Ferroptosis is a novel type of regulated cell death characterized by iron redistribution or accumulation and increased lipid peroxidation in the membrane. Ferroptosis is implicated in many pathological conditions, such as cancer, neurodegenerative diseases, and ischemia-reperfusion injury. In this review, we summarize current research findings on ferroptosis, including possible molecular mechanisms and therapeutic applications of ferroptosis regulators, with a focus on the involvement of ferroptosis in the pathogenesis and treatment of ischemic stroke. Understanding the role of ferroptosis in ischemic stroke will throw some light on the development of methods for diagnosis, treatment, and prevention of this devastating disease.

Keywords: ferroptosis; glutathione; iron; ischemic stroke; lipid peroxidation; treatment.

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Conflict of interest statement

Declaration of Conflicting Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1.
Figure 1.
Regulatory mechanisms of ferroptosis. GPX4 is the pivotal regulator of ferroptosis; the GSH/GPX4 axis is inhibited by system Xc−. PUFAs are metabolized into 4-hydroxynonenal (4-HNE) and malondialdehyde (MDA) in the presence of ·OH, causing lipid peroxidation and ferroptosis. Mitochondria regulate ferroptosis through reactive oxygen species (ROS) production.
Figure 2.
Figure 2.
Iron metabolism and ferritinophagy. Blood Fe2+ can be oxidized to Fe3+, which is transported into cells by Tf-TfR1 and reduced to Fe2+ in acidic endosomes. Intracellular Fe2+ exists in the form of free iron or stored in the ferritin complex, which can be degraded through ferritinophagy; ferroportin 1 transports Fe2+ outside the cell.
See this image and copyright information in PMC

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