Structure, Function, and Pharmacology of Glutamate Receptor Ion Channels.
Structure, Function, and Pharmacology of Glutamate Receptor Ion Channels.
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DOI：
10.1124/pharmrev.120.000131
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发表时间：
2021-10
影响因子：
21.1
通讯作者：
Traynelis SF
中科院分区：
文献类型：
--
作者：
Hansen KB;Wollmuth LP;Bowie D;Furukawa H;Menniti FS;Sobolevsky AI;Swanson GT;Swanger SA;Greger IH;Nakagawa T;McBain CJ;Jayaraman V;Low CM;Dell'Acqua ML;Diamond JS;Camp CR;Perszyk RE;Yuan H;Traynelis SF
L-谷氨酸是哺乳动物中枢神经系统中主要的兴奋性神经递质，其许多生理作用是通过离子型谷氨酸受体 (iGluR) 的信号传导介导的。这些配体门控离子通道对大脑功能至关重要，并且与许多精神和神经系统疾病密切相关。 iGluR 有不同的类别，每一类都有多种受体亚型，在神经元功能中发挥不同的作用。 iGluR 亚型的多样性及其独特的功能特性和生理作用激发了大量研究。自 1989 年克隆第一个 iGluR 亚基基因以来，我们对受体亚型的理解有了很大进展，研究重点已扩展到涵盖最近发现的生物学各个方面，并利用技术进步带来的实验范式。在这里，我们回顾了 3 多年 iGluR 研究的见解，重点关注过去十年所取得的进展。我们涵盖由 18 个离子型谷氨酸受体基因编码的亚基组装而成的所有类别受体的结构、功能、药理学、神经生理学作用以及治疗意义。谷氨酸受体在大脑功能的几乎所有方面都发挥着重要作用，并且参与调节神经系统疾病的一些临床特征或代表治疗的治疗靶点。因此，了解此类受体的结构、功能和药理学将促进我们在分子、细胞和系统水平上对大脑功能的许多方面的理解，并为治疗患者提供新的机会。
Many physiologic effects of l-glutamate, the major excitatory neurotransmitter in the mammalian central nervous system, are mediated via signaling by ionotropic glutamate receptors (iGluRs). These ligand-gated ion channels are critical to brain function and are centrally implicated in numerous psychiatric and neurologic disorders. There are different classes of iGluRs with a variety of receptor subtypes in each class that play distinct roles in neuronal functions. The diversity in iGluR subtypes, with their unique functional properties and physiologic roles, has motivated a large number of studies. Our understanding of receptor subtypes has advanced considerably since the first iGluR subunit gene was cloned in 1989, and the research focus has expanded to encompass facets of biology that have been recently discovered and to exploit experimental paradigms made possible by technological advances. Here, we review insights from more than 3 decades of iGluR studies with an emphasis on the progress that has occurred in the past decade. We cover structure, function, pharmacology, roles in neurophysiology, and therapeutic implications for all classes of receptors assembled from the subunits encoded by the 18 ionotropic glutamate receptor genes. Glutamate receptors play important roles in virtually all aspects of brain function and are either involved in mediating some clinical features of neurological disease or represent a therapeutic target for treatment. Therefore, understanding the structure, function, and pharmacology of this class of receptors will advance our understanding of many aspects of brain function at molecular, cellular, and system levels and provide new opportunities to treat patients.
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作者：
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影响因子：
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作者：
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影响因子：
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作者：
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