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Front Cell Neurosci. 2014 Jun 10;8:160. doi: 10.3389/fncel.2014.00160. eCollection 2014.

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

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Brain Research Centre and Department of Medicine, Vancouver Coastal Health Research Institute, University of British Columbia Vancouver, BC, Canada.


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.


NMDA receptors; dopamine receptors; excitotoxicity; ion channel complex; protein-protein interaction; signaling pathways; synaptic plasticity

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