Targeting Drp1 in Cerebral Ischemia–Reperfusion Injury: Mechanisms and Therapeutic Implications

IF 5 1区医学 Q1 NEUROSCIENCES

CNS Neuroscience & Therapeutics Pub Date : 2025-08-28 DOI:10.1111/cns.70590

Mengnan Liu, Zhixue Yin, Binru Li, Ji Qiu, Dechou Zhang, Raoqiong Wang, Xue Bai, Li Chen

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Abstract

Background

Cerebral ischemia-reperfusion injury (CIRI) arises after blood flow restoration in stroke, where reperfusion paradoxically triggers mitochondrial dysfunction, apoptosis, inflammation, and oxidative stress. Dynamin-related protein 1 (Drp1), a regulator of mitochondrial fission, amplifies these cascades by promoting apoptosis, inflammatory signaling, and calcium imbalance.

Methods

This review synthesizes recent studies on Drp1 in CIRI, focusing on its regulatory roles in mitochondrial dynamics and neuronal injury, and evaluating therapeutic strategies through pharmacological and genetic modulation.

Results

Evidence shows Drp1 inhibition mitigates CIRI in preclinical models by restoring mitochondrial homeostasis, reducing oxidative stress, and improving neuronal survival. Promising interventions include selective inhibitors and genetic approaches, though challenges remain regarding drug specificity, delivery efficiency, and long-term safety.

Conclusion

Drp1 is central to CIRI pathology and represents a promising therapeutic target. Future work should prioritize advanced delivery systems and safer, more selective Drp1 modulators to enable clinical translation.

Abstract Image

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靶向Drp1在脑缺血再灌注损伤中的作用机制及其治疗意义

脑缺血-再灌注损伤（CIRI）发生在脑卒中血流恢复后，其中再灌注矛盾地触发线粒体功能障碍、细胞凋亡、炎症和氧化应激。动力蛋白相关蛋白1 （Drp1）是线粒体分裂的调节因子，通过促进细胞凋亡、炎症信号和钙失衡来放大这些级联反应。方法综述了Drp1在CIRI中的最新研究，重点介绍了Drp1在线粒体动力学和神经元损伤中的调节作用，并评价了通过药理和遗传调控的治疗策略。结果有证据表明，在临床前模型中，Drp1抑制通过恢复线粒体稳态、减少氧化应激和改善神经元存活来减轻CIRI。有希望的干预措施包括选择性抑制剂和遗传方法，尽管在药物特异性、递送效率和长期安全性方面仍然存在挑战。结论Drp1是CIRI病理的核心，是一个有希望的治疗靶点。未来的工作应该优先考虑先进的输送系统和更安全、更有选择性的Drp1调节剂，以实现临床翻译。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

CNS Neuroscience & Therapeutics 医学-神经科学

CiteScore

7.30

自引率

12.70%

发文量

240

审稿时长

2 months

期刊介绍： CNS Neuroscience & Therapeutics provides a medium for rapid publication of original clinical, experimental, and translational research papers, timely reviews and reports of novel findings of therapeutic relevance to the central nervous system, as well as papers related to clinical pharmacology, drug development and novel methodologies for drug evaluation. The journal focuses on neurological and psychiatric diseases such as stroke, Parkinson’s disease, Alzheimer’s disease, depression, schizophrenia, epilepsy, and drug abuse.