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Updated: May 1, 2026
04:48
A High-throughput Calcium-flux Assay to Study NMDA-receptors with Sensitivity to Glycine/D-serine and Glutamate
Published on: July 10, 2018
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Extrasynaptic NMDA receptor involvement in central nervous system disorders.
Matthew P Parsons1, Lynn A Raymond1
1Department of Psychiatry and Brain Research Centre, 2255 Wesbrook Mall, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
Neuron
|April 19, 2014
Summary
Targeting NMDA receptors (NMDARs) may treat neurodegenerative diseases. Overactivated extrasynaptic NMDARs cause toxicity, while synaptic NMDARs promote survival, suggesting localization-based therapies for Alzheimer's and Huntington's diseases.
Area of Science:
- Neuroscience
- Cell Biology
- Pharmacology
Background:
- NMDA receptor (NMDAR)-mediated excitotoxicity contributes to neuronal damage in various neurological conditions.
- Therapeutic targeting of NMDARs is challenging due to their dual role in both excitotoxicity and cell survival/plasticity.
- Emerging evidence suggests a critical role for NMDAR subcellular localization in determining their functional outcome.
Purpose of the Study:
- To review the evidence supporting and refuting the NMDAR localization hypothesis.
- To discuss the implications of NMDAR localization in neurological disorders.
- To explore the potential of targeting NMDAR localization for therapeutic benefit.
Main Methods:
- Literature review of studies investigating NMDAR function and localization.
- Analysis of evidence for and against the localization hypothesis.
- Discussion of NMDAR roles in neurodegenerative diseases, stroke, epilepsy, and TBI.
Main Results:
- Overactivation of extrasynaptic NMDARs is strongly implicated in NMDAR-induced excitotoxicity.
- Physiological activation of synaptic NMDARs is associated with cell survival and plasticity.
- Evidence supports a functional dichotomy based on NMDAR subcellular localization.
Conclusions:
- NMDAR subcellular localization is a critical determinant of its role in neuronal health and disease.
- Targeting excessive extrasynaptic NMDAR activation offers a promising therapeutic strategy.
- Therapeutic interventions focused on NMDAR localization may benefit patients with Alzheimer disease and Huntington disease.
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