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D-Serine, synthesized in the brain by serine racemase from L-serine (its enantiomer), serves as a neuromodulator by coactivating NMDA receptors, making them able to open if they then also bind glutamate. D-serine is a potent agonist at the glycine site (NR1) of the NMDA-type glutamate receptor (NMDAR). For the receptor to open, glutamate and either glycine or D-serine must bind to it; in addition a pore blocker must not be bound (e.g. Mg2+ or Pb2+).

In fact, D-serine is a more potent agonist at the glycine site on the NMDAR than glycine itself.

D-serine was thought to exist only in bacteria until relatively recently; it was the second D amino acid discovered to naturally exist in humans, present as a signalling molecule in the brain, soon after the discovery of D-aspartate. Had D amino acids been discovered in humans sooner, the glycine site on the NMDA receptor might instead be named the D-serine site.

Apart from central nervous system, D-serine plays a signaling role in peripheral tissues and organs such as cartilage, kidney and corpus cavernosum.

Improved synaptic function in the absence of EphB3 results from attenuation in CCI injury-induced synaptic losses and reduced d-serine levels compared with WT injured mice. Together, these findings suggest that EphB3 signaling plays a deleterious role in synaptic stability and plasticity after TBI 1).

Enhanced astrocytic d-serine underlies synaptic damage after traumatic brain injury 2).

Perez EJ, Cepero ML, Perez SU, Coyle JT, Sick TJ, Liebl DJ. EphB3 signaling propagates synaptic dysfunction in the traumatic injured brain. Neurobiol Dis. 2016 Oct;94:73-84. doi: 10.1016/j.nbd.2016.06.007. Epub 2016 Jun 16. PubMed PMID: 27317833.
Perez EJ, Tapanes SA, Loris ZB, Balu DT, Sick TJ, Coyle JT, Liebl DJ. Enhanced astrocytic d-serine underlies synaptic damage after traumatic brain injury. J Clin Invest. 2017 Jul 17. pii: 92300. doi: 10.1172/JCI92300. [Epub ahead of print] PubMed PMID: 28714867.
d_serine.txt · Last modified: 2017/07/19 00:55 by administrador