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Treatment of Cerebral Ischemia Through NMDA Receptors: Metabotropic Signaling and Future Directions
Excessive activation of N-methyl-d-aspartic acid (NMDA) receptors after cerebral ischemia is a key cause of ischemic injury. For a long time, it was generally accepted that calcium influx is a necessary condition for ischemic injury mediated by NMDA receptors. However, recent studies have shown that...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8900870/ https://www.ncbi.nlm.nih.gov/pubmed/35264964 http://dx.doi.org/10.3389/fphar.2022.831181 |
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author | Li, Yuanyuan Cheng, Xiaokun Liu, Xinying Wang, Le Ha, Jing Gao, Zibin He, Xiaoliang Wu, Zhuo Chen, Aibing Jewell, Linda L. Sun, Yongjun |
author_facet | Li, Yuanyuan Cheng, Xiaokun Liu, Xinying Wang, Le Ha, Jing Gao, Zibin He, Xiaoliang Wu, Zhuo Chen, Aibing Jewell, Linda L. Sun, Yongjun |
author_sort | Li, Yuanyuan |
collection | PubMed |
description | Excessive activation of N-methyl-d-aspartic acid (NMDA) receptors after cerebral ischemia is a key cause of ischemic injury. For a long time, it was generally accepted that calcium influx is a necessary condition for ischemic injury mediated by NMDA receptors. However, recent studies have shown that NMDA receptor signaling, independent of ion flow, plays an important role in the regulation of ischemic brain injury. The purpose of this review is to better understand the roles of metabotropic NMDA receptor signaling in cerebral ischemia and to discuss the research and development directions of NMDA receptor antagonists against cerebral ischemia. This mini review provides a discussion on how metabotropic transduction is mediated by the NMDA receptor, related signaling molecules, and roles of metabotropic NMDA receptor signaling in cerebral ischemia. In view of the important roles of metabotropic signaling in cerebral ischemia, NMDA receptor antagonists, such as GluN2B-selective antagonists, which can effectively block both pro-death metabotropic and pro-death ionotropic signaling, may have better application prospects. |
format | Online Article Text |
id | pubmed-8900870 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-89008702022-03-08 Treatment of Cerebral Ischemia Through NMDA Receptors: Metabotropic Signaling and Future Directions Li, Yuanyuan Cheng, Xiaokun Liu, Xinying Wang, Le Ha, Jing Gao, Zibin He, Xiaoliang Wu, Zhuo Chen, Aibing Jewell, Linda L. Sun, Yongjun Front Pharmacol Pharmacology Excessive activation of N-methyl-d-aspartic acid (NMDA) receptors after cerebral ischemia is a key cause of ischemic injury. For a long time, it was generally accepted that calcium influx is a necessary condition for ischemic injury mediated by NMDA receptors. However, recent studies have shown that NMDA receptor signaling, independent of ion flow, plays an important role in the regulation of ischemic brain injury. The purpose of this review is to better understand the roles of metabotropic NMDA receptor signaling in cerebral ischemia and to discuss the research and development directions of NMDA receptor antagonists against cerebral ischemia. This mini review provides a discussion on how metabotropic transduction is mediated by the NMDA receptor, related signaling molecules, and roles of metabotropic NMDA receptor signaling in cerebral ischemia. In view of the important roles of metabotropic signaling in cerebral ischemia, NMDA receptor antagonists, such as GluN2B-selective antagonists, which can effectively block both pro-death metabotropic and pro-death ionotropic signaling, may have better application prospects. Frontiers Media S.A. 2022-02-21 /pmc/articles/PMC8900870/ /pubmed/35264964 http://dx.doi.org/10.3389/fphar.2022.831181 Text en Copyright © 2022 Li, Cheng, Liu, Wang, Ha, Gao, He, Wu, Chen, Jewell and Sun. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Pharmacology Li, Yuanyuan Cheng, Xiaokun Liu, Xinying Wang, Le Ha, Jing Gao, Zibin He, Xiaoliang Wu, Zhuo Chen, Aibing Jewell, Linda L. Sun, Yongjun Treatment of Cerebral Ischemia Through NMDA Receptors: Metabotropic Signaling and Future Directions |
title | Treatment of Cerebral Ischemia Through NMDA Receptors: Metabotropic Signaling and Future Directions |
title_full | Treatment of Cerebral Ischemia Through NMDA Receptors: Metabotropic Signaling and Future Directions |
title_fullStr | Treatment of Cerebral Ischemia Through NMDA Receptors: Metabotropic Signaling and Future Directions |
title_full_unstemmed | Treatment of Cerebral Ischemia Through NMDA Receptors: Metabotropic Signaling and Future Directions |
title_short | Treatment of Cerebral Ischemia Through NMDA Receptors: Metabotropic Signaling and Future Directions |
title_sort | treatment of cerebral ischemia through nmda receptors: metabotropic signaling and future directions |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8900870/ https://www.ncbi.nlm.nih.gov/pubmed/35264964 http://dx.doi.org/10.3389/fphar.2022.831181 |
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