The NMDA receptor complex: a multifunctional machine at the glutamatergic synapse.

The NMDA receptor complex: a multifunctional machine at the glutamatergic synapse.
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DOI:
10.3389/fncel.2014.00160
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发表时间:
2014
影响因子:
5.3
通讯作者:
Wang YT
Wang YT
中科院分区:
医学2区
文献类型:
--
作者:
Fan X;Jin WY;Wang YT

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N-甲基-D-天冬氨酸受体(NMDAR)是一个大的多蛋白复合物的一部分,在神经元突触。NMDAR与突触蛋白的组装提供了调节NMDAR通道特性和受体运输的手段,并将NMDAR活化与不同的细胞内信号传导途径偶联,从而有助于NMDAR功能的多功能性。突触处的受体-蛋白质相互作用提供了用于调节突触功效的动态和强大的机制,但也可在病理条件下促成NMDAR过度激活诱导的兴奋性毒性和细胞损伤。一个新兴的概念是,通过了解NMDAR复合物中疾病特异性蛋白质-蛋白质相互作用的机制和功能,我们可能能够开发基于蛋白质-NMDAR相互作用的新疗法,用于治疗NMDAR功能障碍是其发病机制根源的脑疾病。
The N-methyl-D-aspartate receptors (NMDARs) are part of a large multiprotein complex at the glutamatergic synapse. The assembly of NMDARs with synaptic proteins offers a means to regulate NMDAR channel properties and receptor trafficking, and couples NMDAR activation to distinct intracellular signaling pathways, thus contributing to the versatility of NMDAR functions. Receptor-protein interactions at the synapse provide a dynamic and powerful mechanism for regulating synaptic efficacy, but can also contribute to NMDAR overactivation-induced excitotoxicity and cellular damage under pathological conditions. An emerging concept is that by understanding the mechanisms and functions of disease-specific protein-protein interactions in the NMDAR complex, we may be able to develop novel therapies based on protein-NMDAR interactions for the treatment of brain diseases in which NMDAR dysfunction is at the root of their pathogenesis.
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