Ge Yang, Wang Yu Tian
Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, BC, Canada.
Department of Medicine, University of British Columbia, Vancouver, BC, Canada.
Front Mol Neurosci. 2023 May 31;16:1190324. doi: 10.3389/fnmol.2023.1190324. eCollection 2023.
Glutamate N-methyl-D-aspartate receptor (NMDAR) is critical for promoting physiological synaptic plasticity and neuronal viability. As a major subpopulation of the NMDAR, the GluN2B subunit-containing NMDARs have distinct pharmacological properties, physiological functions, and pathological relevance to neurological diseases compared with other NMDAR subtypes. In mature neurons, GluN2B-containing NMDARs are likely expressed as both diheteromeric and triheteromeric receptors, though the functional importance of each subpopulation has yet to be disentangled. Moreover, the C-terminal region of the GluN2B subunit forms structural complexes with multiple intracellular signaling proteins. These protein complexes play critical roles in both activity-dependent synaptic plasticity and neuronal survival and death signaling, thus serving as the molecular substrates underlying multiple physiological functions. Accordingly, dysregulation of GluN2B-containing NMDARs and/or their downstream signaling pathways has been implicated in neurological diseases, and various strategies to reverse these deficits have been investigated. In this article, we provide an overview of GluN2B-containing NMDAR pharmacology and its key physiological functions, highlighting the importance of this receptor subtype during both health and disease states.
谷氨酸N-甲基-D-天冬氨酸受体（NMDAR）对于促进生理性突触可塑性和神经元活力至关重要。作为NMDAR的一个主要亚群，与其他NMDAR亚型相比，含GluN2B亚基的NMDAR具有独特的药理学特性、生理功能以及与神经疾病的病理相关性。在成熟神经元中，含GluN2B的NMDAR可能以双异聚体和三异聚体受体的形式表达，尽管每个亚群的功能重要性尚未完全厘清。此外，GluN2B亚基的C末端区域与多种细胞内信号蛋白形成结构复合物。这些蛋白复合物在活性依赖的突触可塑性以及神经元存活和死亡信号传导中均发挥关键作用，因此作为多种生理功能的分子基础。相应地，含GluN2B的NMDAR及其下游信号通路的失调与神经疾病有关，并且已经研究了各种逆转这些缺陷的策略。在本文中，我们概述了含GluN2B的NMDAR药理学及其关键生理功能，强调了该受体亚型在健康和疾病状态下的重要性。
