Department of Medicinal Chemistry, Faculty of Pharmaceutical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark.
Neuropharmacology. 2011 Jan;60(1):135-50. doi: 10.1016/j.neuropharm.2010.08.004. Epub 2010 Aug 14.
Ionotropic glutamate receptors (iGluRs) constitute a family of ligand-gated ion channels that are essential for mediating fast synaptic transmission in the central nervous system. These receptors play an important role for the development and function of the nervous system, and are essential in learning and memory. However, iGluRs are also implicated in or have causal roles for several brain disorders, e.g. epilepsy, Alzheimer's disease, Parkinson's disease and schizophrenia. Their involvement in neurological diseases has stimulated widespread interest in their structure and function. Since the first publication in 1998 of the structure of a recombinant soluble protein comprising the ligand-binding domain of GluA2 extensive studies have afforded numerous crystal structures of wildtype and mutant proteins including different ligands. The structural information obtained combined with functional data have led to models for receptor activation and desensitization by agonists, inhibition by antagonists and block of desensitization by positive allosteric modulators. Furthermore, the structural and functional studies have formed a powerful platform for the design of new selective compounds.
离子型谷氨酸受体 (iGluRs) 是一类配体门控离子通道，对于介导中枢神经系统中的快速突触传递至关重要。这些受体在神经系统的发育和功能中发挥着重要作用，并且在学习和记忆中必不可少。然而，iGluRs 也与几种脑部疾病有关，例如癫痫、阿尔茨海默病、帕金森病和精神分裂症。它们在神经疾病中的参与激发了人们对其结构和功能的广泛兴趣。自 1998 年首次发表包含 GluA2 配体结合域的重组可溶性蛋白的结构以来，已经有大量关于野生型和突变型蛋白（包括不同配体）的晶体结构的研究。获得的结构信息与功能数据相结合，为激动剂诱导的受体激活和脱敏、拮抗剂抑制以及正变构调节剂阻断脱敏等提供了模型。此外，结构和功能研究为新型选择性化合物的设计提供了强大的平台。
