Research Progress of PSD-95-Targeted Brain Cytoprotective Agents in Acute Ischemic Stroke Based on STAIR Principles

doi:10.3969/j.issn.1673-5765.2026.05.004

Abstract

Abstract: Brain cytoprotection serves as an important complementary strategy to reperfusion therapy in acute ischemic stroke. To overcome the challenges in the clinical translation of brain cytoprotective agents, the stroke therapy academic industry roundtable (STAIR) was established in 1999 in the United States with the aim of developing a systematic framework to guide drug research and development in stroke. Since its inception, STAIR has continuously refined strategy-specific recommendations for brain cytoprotective agents, providing structured guidance for preclinical experimentation and clinical research. Postsynaptic density protein-95 (PSD-95) has emerged as a key target in the brain cytoprotection field owing to its well-defined mechanisms and high target specificity. Under the guidance of STAIR principles, PSD-95-based brain cytoprotective agents have undergone a series of preclinical and clinical studies. This paper systematically reviews the key points of STAIR principles for the development of brain cytoprotective agents and summarizes the status of preclinical and clinical studies of PSD-95-targeting agents under STAIR guidance. It also outlines the research progress on the brain cytoprotective effects of these agents in acute ischemic stroke, thereby providing a reference for the clinical translation of brain cytoprotective agents.

Key words: Acute ischemic stroke; Stroke therapy academic industry roundtable; Postsynaptic density protein-95; Brain cytoprotective agent; Nerinetide; Loberamisal

摘要： 脑细胞保护是急性缺血性卒中再灌注治疗的重要补充策略。为打破脑细胞保护剂的临床转化困境，美国卒中治疗学术产业圆桌会议（stroke therapy academic industry roundtable，STAIR）于1999年成立，致力于建立卒中领域药物研发的系统化指导框架。自成立以来，STAIR不断完善针对脑细胞保护剂的研发策略及相关临床前实验、临床研究的系统性指导建议。突触后致密区95（postsynaptic density-95，PSD-95）因作用机制明确、靶点特异性高，已成为脑细胞保护领域的关键靶点之一。在STAIR原则的指导下，基于PSD-95靶点的脑细胞保护剂已完成了一系列临床前实验和临床研究。本文系统梳理STAIR原则指导脑细胞保护剂研发的要点，以及基于STAIR原则的PSD-95靶向药物临床前实验和临床研究的开展情况，总结其对缺血性卒中脑细胞保护作用的研究进展，以期为脑细胞保护剂的临床转化提供参考。

关键词: 急性缺血性卒中; 卒中治疗学术产业圆桌会议; 突触后致密区95; 脑细胞保护剂; 奈瑞奈肽; 洛贝米柳

CLC Number:

HE Dandan, LI Shuya. Research Progress of PSD-95-Targeted Brain Cytoprotective Agents in Acute Ischemic Stroke Based on STAIR Principles[J]. Chinese Journal of Stroke, 2026, 21(5): 543-552.

何丹丹, 李姝雅. 基于STAIR原则的PSD-95靶向脑细胞保护剂在急性缺血性卒中中的研究进展[J]. 中国卒中杂志, 2026, 21(5): 543-552.

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URL: https://www.chinastroke.org.cn/EN/10.3969/j.issn.1673-5765.2026.05.004

https://www.chinastroke.org.cn/EN/Y2026/V21/I5/543

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