NMDA Receptor C-Terminal Domain Signalling in Development, Maturity, and Disease
Abstract
:1. Introduction
2. The Role of the CTD in Developmental and Activity-Dependent Changes in NMDAR Subunit Composition
3. GluN2A/2B CTD Mutations Associated with Neurodevelopmental Disorders
4. A Critical Role for CTD Interactions in Acute Excitotoxicity
4.1. GluN2B Mediated Excitotoxicity through PSD95-nNOS Pathway
4.2. The Role of Extrasynaptic Specific Physical and Functional Coupling in Excitotoxicity
4.3. DAPK1 Interactions at CTD2B Do Not Mediate Excitotoxic Cell Death
4.4. Role of GluN2A and GluN2B in Tissue-Type Plasminogen Activator Mediated Neuroprotection
5. Role of CTD2B in Alzheimer’s Disease?
5.1. Role of CTD2B in Ionotropic and Metabotropic Dependent Pathways in AD
5.2. Implications for Astrocytic NMDA Subunits in AD?
6. Contribution of CTD2A and CTD2B in Other Disease Pathologies?
7. Concluding Remarks
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Model | Treatment | Findings | Study |
---|---|---|---|
HEK293 | Coexpression of GluN1/GluN2B and constitutively active DAPK1 | ↑ GluN1/GluN2B peak amplitude of receptor currents ↑ S1303 phosphorylation | [103] |
DAPK1+/+ cortical neurons | OGD | ↑ S1303 phosphorylation ↑ amplitude of extrasynaptic NMDA mediated currents and Ca2+ transients | [103] |
DAPK1+/+ cortical neurons | Bath application of NMDA (20 µM and 50 µM) and OGD | No change in s1303 phosphorylation | [104] |
DAPK1−/− cortical neurons | OGD | No change in s1301 phosphorylation | [103] |
DAPK1−/− in vivo | MCAO | ↓ infarct volume as measured by TTC staining | [103] |
DAPK1−/− in vivo | MCAO | No change to infarct volume as measured by H-E staining | [104] |
DAPK1+/+ in vivo | CA/CPR | No change in s1303 phosphorylation | [105] |
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Haddow, K.; Kind, P.C.; Hardingham, G.E. NMDA Receptor C-Terminal Domain Signalling in Development, Maturity, and Disease. Int. J. Mol. Sci. 2022, 23, 11392. https://doi.org/10.3390/ijms231911392
Haddow K, Kind PC, Hardingham GE. NMDA Receptor C-Terminal Domain Signalling in Development, Maturity, and Disease. International Journal of Molecular Sciences. 2022; 23(19):11392. https://doi.org/10.3390/ijms231911392
Chicago/Turabian StyleHaddow, Kirsty, Peter C. Kind, and Giles E. Hardingham. 2022. "NMDA Receptor C-Terminal Domain Signalling in Development, Maturity, and Disease" International Journal of Molecular Sciences 23, no. 19: 11392. https://doi.org/10.3390/ijms231911392
APA StyleHaddow, K., Kind, P. C., & Hardingham, G. E. (2022). NMDA Receptor C-Terminal Domain Signalling in Development, Maturity, and Disease. International Journal of Molecular Sciences, 23(19), 11392. https://doi.org/10.3390/ijms231911392