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

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 treatmen...

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Autores principales: Lu, Yingyu, Zhou, Wanlu, Cui, Qinghua, Cui, Chunmei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10418587/
https://www.ncbi.nlm.nih.gov/pubmed/37569618
http://dx.doi.org/10.3390/ijms241512244
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author Lu, Yingyu
Zhou, Wanlu
Cui, Qinghua
Cui, Chunmei
author_facet Lu, Yingyu
Zhou, Wanlu
Cui, Qinghua
Cui, Chunmei
author_sort Lu, Yingyu
collection PubMed
description 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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spelling pubmed-104185872023-08-12 G Protein-Coupled Receptor 40 Agonist LY2922470 Alleviates Ischemic-Stroke-Induced Acute Brain Injury and Functional Alterations in Mice Lu, Yingyu Zhou, Wanlu Cui, Qinghua Cui, Chunmei Int J Mol Sci Communication 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. MDPI 2023-07-31 /pmc/articles/PMC10418587/ /pubmed/37569618 http://dx.doi.org/10.3390/ijms241512244 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Communication
Lu, Yingyu
Zhou, Wanlu
Cui, Qinghua
Cui, Chunmei
G Protein-Coupled Receptor 40 Agonist LY2922470 Alleviates Ischemic-Stroke-Induced Acute Brain Injury and Functional Alterations in Mice
title G Protein-Coupled Receptor 40 Agonist LY2922470 Alleviates Ischemic-Stroke-Induced Acute Brain Injury and Functional Alterations in Mice
title_full G Protein-Coupled Receptor 40 Agonist LY2922470 Alleviates Ischemic-Stroke-Induced Acute Brain Injury and Functional Alterations in Mice
title_fullStr G Protein-Coupled Receptor 40 Agonist LY2922470 Alleviates Ischemic-Stroke-Induced Acute Brain Injury and Functional Alterations in Mice
title_full_unstemmed G Protein-Coupled Receptor 40 Agonist LY2922470 Alleviates Ischemic-Stroke-Induced Acute Brain Injury and Functional Alterations in Mice
title_short G Protein-Coupled Receptor 40 Agonist LY2922470 Alleviates Ischemic-Stroke-Induced Acute Brain Injury and Functional Alterations in Mice
title_sort g protein-coupled receptor 40 agonist ly2922470 alleviates ischemic-stroke-induced acute brain injury and functional alterations in mice
topic Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10418587/
https://www.ncbi.nlm.nih.gov/pubmed/37569618
http://dx.doi.org/10.3390/ijms241512244
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