D-serine: physiology and pathology.

Here, we discuss the recent data on the role of different N-methyl D-aspartate receptor (NMDAR) coagonists, D-serine and glycine, in regulating NMDAR activity and neurotoxicity. D-Serine originates from both neurons and astrocytes, from where it is released by different mechanisms. Recent data indicate that like glial D-serine, neuronal D-serine is required for NMDAR-dependent, long-term potentiation at the hippocampal CA1-CA3 synapses and proper synapse formation in the cerebral cortex. D-serine is the physiological coagonist of synaptic NMDAR, whereas glycine action is restricted to extrasynaptic sites. D-Serine is now recognized as the major NMDAR coagonist at the synapse. The data establish D-serine as a key transmitter or neuromodulator that mediates synaptic NMDAR activation and neurotoxicity. In this context, drugs that inhibit D-serine synthesis or release will provide new neuroprotective strategy.

Citation

Inna Radzishevsky, Hagit Sason, Herman Wolosker. D-serine: physiology and pathology. Current opinion in clinical nutrition and metabolic care. 2013 Jan;16(1):72-5

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PMID: 23041616

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