G Protein-Coupled Receptor 40 Agonist LY2922470 Alleviates Ischemic-Stroke-Induced Acute Brain Injury and Functional Alterations in Mice

被引:2
|
作者
Lu, Yingyu [1 ]
Zhou, Wanlu [1 ]
Cui, Qinghua [1 ]
Cui, Chunmei [1 ]
机构
[1] Peking Univ, Sch Basic Med Sci, Dept Biomed Informat, State Key Lab Vasc Homeostasis & Remodeling, 38 Xueyuan Rd, Beijing 100191, Peoples R China
关键词
stroke; LY2922470; ischemic stroke; EPIDEMIOLOGY; MANAGEMENT; DISCOVERY; POTENT; HEART;
D O I
10.3390/ijms241512244
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Stroke is a major cause of fatalities and disabilities around the world, yet the available treatments for it are still limited. The quest for more efficacious drugs and therapies is still an arduous task. LY2922470 is currently used as a G protein-coupled receptor 40 (GPR40) agonist for the treatment of type 2 diabetes. Previous studies have reported protective effects of other GPR40 activators on the brain; however, it remains unclear whether LY2922470 could be a new stroke therapy and improve the stroke-induced brain damage. Here, we first reveal that the transcriptomic gene signature induced by LY2922470 is highly similar to those induced by some agents being involved in defending from cerebrovascular accidents and transient ischemic attacks, including acetylsalicylic acid, progesterone, estradiol, dipyridamole, and dihydroergotamine. This result thus suggests that LY2922470 could have protective effects against ischemic stroke. As a result, further experiments show that giving the small molecule LY2922470 via oral administration or intraperitoneal injection was seen to have a positive effect on neuroprotection with a reduction in infarct size and an improvement in motor skills in mice. Finally, it was demonstrated that LY2922470 could successfully mitigate the harm to the brain caused by ischemic stroke.
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页数:8
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