GluN2B-containing NMDARs in the mammalian brain: pharmacology, physiology, and pathology
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 relevanc...
| Main Authors: | , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2023-05-01
|
| Series: | Frontiers in Molecular Neuroscience |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fnmol.2023.1190324/full |
| _version_ | 1827937961742696448 |
|---|---|
| author | Yang Ge Yang Ge Yu Tian Wang Yu Tian Wang |
| author_facet | Yang Ge Yang Ge Yu Tian Wang Yu Tian Wang |
| author_sort | Yang Ge |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-13T08:33:05Z |
| format | Article |
| id | doaj.art-a09fd18dccd14076a1036d7a10a71699 |
| institution | Directory Open Access Journal |
| issn | 1662-5099 |
| language | English |
| last_indexed | 2024-03-13T08:33:05Z |
| publishDate | 2023-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Neuroscience |
| spelling | doaj.art-a09fd18dccd14076a1036d7a10a716992023-05-31T04:16:37ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992023-05-011610.3389/fnmol.2023.11903241190324GluN2B-containing NMDARs in the mammalian brain: pharmacology, physiology, and pathologyYang Ge0Yang Ge1Yu Tian Wang2Yu Tian Wang3Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, BC, CanadaDepartment of Medicine, University of British Columbia, Vancouver, BC, CanadaDjavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, BC, CanadaDepartment of Medicine, University of British Columbia, Vancouver, BC, CanadaGlutamate 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.https://www.frontiersin.org/articles/10.3389/fnmol.2023.1190324/fullNMDAR (NMDA receptor)GluN2B (NMDA receptor subunit NR2B)synaptic plasticity (LTP/LTD)neuronal deathneurological disorders |
| spellingShingle | Yang Ge Yang Ge Yu Tian Wang Yu Tian Wang GluN2B-containing NMDARs in the mammalian brain: pharmacology, physiology, and pathology Frontiers in Molecular Neuroscience NMDAR (NMDA receptor) GluN2B (NMDA receptor subunit NR2B) synaptic plasticity (LTP/LTD) neuronal death neurological disorders |
| title | GluN2B-containing NMDARs in the mammalian brain: pharmacology, physiology, and pathology |
| title_full | GluN2B-containing NMDARs in the mammalian brain: pharmacology, physiology, and pathology |
| title_fullStr | GluN2B-containing NMDARs in the mammalian brain: pharmacology, physiology, and pathology |
| title_full_unstemmed | GluN2B-containing NMDARs in the mammalian brain: pharmacology, physiology, and pathology |
| title_short | GluN2B-containing NMDARs in the mammalian brain: pharmacology, physiology, and pathology |
| title_sort | glun2b containing nmdars in the mammalian brain pharmacology physiology and pathology |
| topic | NMDAR (NMDA receptor) GluN2B (NMDA receptor subunit NR2B) synaptic plasticity (LTP/LTD) neuronal death neurological disorders |
| url | https://www.frontiersin.org/articles/10.3389/fnmol.2023.1190324/full |
| work_keys_str_mv | AT yangge glun2bcontainingnmdarsinthemammalianbrainpharmacologyphysiologyandpathology AT yangge glun2bcontainingnmdarsinthemammalianbrainpharmacologyphysiologyandpathology AT yutianwang glun2bcontainingnmdarsinthemammalianbrainpharmacologyphysiologyandpathology AT yutianwang glun2bcontainingnmdarsinthemammalianbrainpharmacologyphysiologyandpathology |