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A new specific GluN2B partial antagonist ameliorates brain injury caused by ischemic stroke in rats

文献类型：期刊论文

作者Fan, Yanhua5,6; Wu, Hongshan5,6; Yin, Dan4; Liu, Qianjun2,3; Yuan, Changgen2,3; Zhong, Ting5,6; Xia, Baijuan4; Xiong, Liang5,6; Li, Yi6; Zeng, Lei6
刊名BIOORGANIC CHEMISTRY
出版日期2025-07-01
卷号161页码:15
关键词FLY26 GluN2B partial antagonists Ischemic stroke BDNF/TrkB signaling pathway
ISSN号0045-2068
DOI10.1016/j.bioorg.2025.108547
英文摘要Ischemic stroke is one of the top-ranked causes of death and disability in the world, but still lacking efficacy treatment options. Excitotoxicity caused by NMDA receptors (NMDARs) hyperactivation plays a key role in brain injury after ischemic stroke. GluN2B, the regulatory subunit of NMDARs, plays an important role in brain injury induced by ischemic stroke, and specific antagonists of GluN2B can ameliorate brain damage induced by ischemic stroke in rats. However, over half a century after Memantine (the first NMDA partial inhibitor for Alzheimer's clinical treatment) was identified, only a few additional NMDA partial inhibitors, especially those specifically targeting GluN2B, have been discovered. In this study, by using whole patch-clamp technique and multiple molecular biological methods, we discovered a new specific GluN2B partial antagonist, named FLY26, and further determined its effects on alleviating the brain injury caused by ischemic stroke in rats. Our experiment results showed FLY26 suppressed the excitotoxicity caused by overactivation of NMDARs in SH-SY5Y cells, and ameliorated brain damage of middle cerebral artery occlusion (MACO) rats, within the dosage range of 1.5-6.0 mg/kg, via BDNF/TrkB signaling pathway. Our results indicated that FLY26 is a promising lead compound for the development of novel, specific GluN2B partial antagonist. Our results indicated that FLY26 is a promising lead compound for the development of novel, specific GluN2B partial antagonist, which may offer better safety profile as a therapeutic intervention for ischemic stroke.
WOS关键词RECEPTOR ; EXPRESSION ; MEMANTINE ; DISEASE ; MEMORY ; DEATH
资助项目National Natural Science Foundation of China[81960632] ; National Natural Science Foundation of China[31671049] ; National Natural Science Foundation of China[32371005] ; High-level Innovative Talents Fund of Guizhou Province[GCC [2023] 002] ; Guizhou Science and Technology Support Project[Qiankehe [2025] 114] ; Thousands of Innovative Talents of Guizhou Province[GZQ202006081] ; Shanghai Municipal Science and Technology Major Project[184319071000] ; Shanghai Municipal Science and Technology Major Project[19140903102]
WOS研究方向Biochemistry & Molecular Biology ; Chemistry
语种英语
WOS记录号WOS:001486841200001
出版者ACADEMIC PRESS INC ELSEVIER SCIENCE
源URL[http://119.78.100.183/handle/2S10ELR8/317905]  
专题新药研究国家重点实验室
通讯作者Li, Yang; Li, Yixin; Tang, Lei
作者单位1.Fudan Univ, Huashan Hosp, Natl Clin Res Ctr Aging & Med, Shanghai 200040, Peoples R China
2.Nanchang Univ, Sch Pharm, Nanchang 330006, Peoples R China
3.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
4.Guizhou Med Univ, Sch Basic Med Sci, Dept Histol & Embryol, Guiyang 550025, Guizhou, Peoples R China
5.Nat Prod Res Ctr Guizhou Prov, Guiyang 550014, Peoples R China
6.Guizhou Med Univ, State Key Lab Discovery & Utilizat Funct Component, Guiyang 550014, Peoples R China
推荐引用方式
GB/T 7714		 Fan, Yanhua,Wu, Hongshan,Yin, Dan,et al. A new specific GluN2B partial antagonist ameliorates brain injury caused by ischemic stroke in rats[J]. BIOORGANIC CHEMISTRY,2025,161:15.
APA Fan, Yanhua.,Wu, Hongshan.,Yin, Dan.,Liu, Qianjun.,Yuan, Changgen.,...&Tang, Lei.(2025).A new specific GluN2B partial antagonist ameliorates brain injury caused by ischemic stroke in rats.BIOORGANIC CHEMISTRY,161,15.
MLA Fan, Yanhua,et al."A new specific GluN2B partial antagonist ameliorates brain injury caused by ischemic stroke in rats".BIOORGANIC CHEMISTRY 161(2025):15.

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来源：上海药物研究所

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