New insights in ferroptosis: Potential therapeutic targets for the treatment of ischemic stroke

Ziqing Wei; Yi Xie; Mingze Wei; Huijuan Zhao; Kaidi Ren; Qi Feng; Yuming Xu

doi:10.3389/fphar.2022.1020918

New insights in ferroptosis: Potential therapeutic targets for the treatment of ischemic stroke

Front Pharmacol. 2022 Nov 8:13:1020918. doi: 10.3389/fphar.2022.1020918. eCollection 2022.

Authors

Ziqing Wei^{1

2

3}, Yi Xie^{1

2}, Mingze Wei⁴, Huijuan Zhao⁵, Kaidi Ren^{6

7

8}, Qi Feng^{9

10

11}, Yuming Xu^{1

2}

Affiliations

¹ Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
² Henan Key Laboratory of Cerebrovascular Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
³ Clinical Systems Biology Laboratories, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
⁴ The Second Clinical Medical College, Harbin Medical University, Harbin, China.
⁵ Henan International Joint Laboratory of Thrombosis and Hemostasis, Basic Medical College, Henan University of Science and Technology, Luoyang, China.
⁶ Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
⁷ Henan Key Laboratory of Precision Clinical Pharmacy, Zhengzhou, China.
⁸ Henan Engineering Research Center for Application & Translation of Precision Clinical Pharmacy, Zhengzhou University, Zhengzhou, China.
⁹ Research Institute of Nephrology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
¹⁰ Department of Integrated Traditional and Western Nephrology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
¹¹ Henan Province Research Center for Kidney Disease, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Abstract

Stroke is a common disease in clinical practice, which seriously endangers people's physical and mental health. The neurovascular unit (NVU) plays a key role in the occurrence and development of ischemic stroke. Different from other classical types of cell death such as apoptosis, necrosis, autophagy, and pyroptosis, ferroptosis is an iron-dependent lipid peroxidation-driven new form of cell death. Interestingly, the function of NVU and stroke development can be regulated by activating or inhibiting ferroptosis. This review systematically describes the NVU in ischemic stroke, provides a comprehensive overview of the regulatory mechanisms and key regulators of ferroptosis, and uncovers the role of ferroptosis in the NVU and the progression of ischemic stroke. We further discuss the latest progress in the intervention of ferroptosis as a therapeutic target for ischemic stroke and summarize the research progress and regulatory mechanism of ferroptosis inhibitors on stroke. In conclusion, ferroptosis, as a new form of cell death, plays a key role in ischemic stroke and is expected to become a new therapeutic target for this disease.

Keywords: ferroptosis; inhibitors; neurovascular unit (NVU); stroke; therapeutic target.

Publication types

Review