D-Serine Regulation of NMDA Receptor Activity

@article{Wolosker2006DSerineRO,
  title={D-Serine Regulation of NMDA Receptor Activity},
  author={Herman Wolosker},
  journal={Science's STKE},
  year={2006},
  volume={2006},
  pages={pe41 - pe41}
}
The N-Methyl-D-aspartate–type glutamate receptor (NMDAR) plays a key role in several important processes involving the nervous system, including brain development, synaptic plasticity, and learning. Unlike other neurotransmitter receptors, which are activated by individual neurotransmitters, activation of NMDARs requires the binding of a coagonist (D-serine or glycine) in addition to glutamate. Although previously considered an "unnatural" amino acid, D-serine is a key regulator of NMDAR… 
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References

SHOWING 1-10 OF 48 REFERENCES
D-serine, an endogenous synaptic modulator: localization to astrocytes and glutamate-stimulated release.
TLDR
D-Serine appears to be the endogenous ligand for the glycine site of NMDA receptors, suggesting a mechanism by which astrocyte-derived D-serine could modulate neurotransmission.
Neuron-derived D-Serine Release Provides a Novel Means to Activate N-Methyl-D-aspartate Receptors*
TLDR
The results suggest that neurons are a major source of d-Serine, and Glutamate-induced neuronal d-serine release provides a novel mechanism for activating NMDA receptors by an autocrine or paracrine way.
d-serine and serine racemase are present in the vertebrate retina and contribute to the physiological activation of NMDA receptors
TLDR
Physiological studies in rats and salamanders demonstrated that, in retinal ganglion cells, d-serine can enhance excitatory currents elicited by the application of NMDA, as well as the NMDA receptor component of light-evoked synaptic responses, raising the possibility that endogenous d-Serine serves as a ligand for setting the sensitivity ofNMDA receptors under physiological conditions.
D-serine is an endogenous ligand for the glycine site of the N-methyl-D-aspartate receptor.
TLDR
D-serine is an endogenous modulator of the glycine site of NMDA receptors and fully occupies this site at some functional synapses and greatly attenuates NMDA receptor-mediated neurotransmission as assessed by using whole-cell patch-clamp recordings or indirectly by using biochemical assays of the sequelae of NMda receptor- mediated calcium flux.
Glial transport of the neuromodulator d-serine
Neurobiology through the looking-glass: d-serine as a new glial-derived transmitter
Serine racemase: a glial enzyme synthesizing D-serine to regulate glutamate-N-methyl-D-aspartate neurotransmission.
TLDR
Cloning and expression of serine racemase in the brain demonstrates the conservation of D-amino acid metabolism in mammals with implications for the regulation of N-methyl-D-aspartate neurotransmission through glia-neuronal interactions.
D-Serine Is the Dominant Endogenous Coagonist for NMDA Receptor Neurotoxicity in Organotypic Hippocampal Slices
TLDR
The data indicate that d-serine is the dominant coagonist for NMDA receptor-elicited neurotoxicity, mediating all cell death elicited by NMDA in organotypic slices, and suggests an essential role for this unusual d-amino acid, with implications for the mechanism of neuronal death in the nervous system.
Serine racemase: activation by glutamate neurotransmission via glutamate receptor interacting protein and mediation of neuronal migration.
TLDR
In neuronal migration, glutamate stimulates Bergmann glia to form and release D-serine, which, together with glutamate, activates NMDA receptors on granule neurons, chemokinetically enhancing migration.
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