D-amino acids in the brain: D-serine in neurotransmission and neurodegeneration

Herman Wolosker, Elena Dumin, Livia Balan, Veronika N. Foltyn

Research output: Contribution to journalShort surveypeer-review

253 Scopus citations

Abstract

The mammalian brain contains unusually high levels of D-serine, a D-amino acid previously thought to be restricted to some bacteria and insects. In the last few years, studies from several groups have demonstrated that D-serine is a physiological co-agonist of the N-methyl D-aspartate (NMDA) type of glutamate receptor - a key excitatory neurotransmitter receptor in the brain. D-Serine binds with high affinity to a co-agonist site at the NMDA receptors and, along with glutamate, mediates several important physiological and pathological processes, including NMDA receptor transmission, synaptic plasticity and neurotoxicity. In recent years, biosynthetic, degrada-tive and release pathways for D-serine have been identified, indicating that D-serine may function as a transmitter. At first, D-serine was described in astrocytes, a class of glial cells that ensheathes neurons and release several transmitters that modulate neurotransmission. This led to the notion that D-serine is a glia-derived transmitter (or gliotransmitter). However, recent data indicate that serine racemase, the D-serine biosynthetic enzyme, is widely expressed in neurons of the brain, suggesting that D-serine also has a neuronal origin. We now review these findings, focusing on recent questions regarding the roles of glia versus neurons in D-serine signaling.

Original languageEnglish
Pages (from-to)3514-3526
Number of pages13
JournalFEBS Journal
Volume275
Issue number14
DOIs
StatePublished - Jul 2008

Keywords

  • D-serine
  • Gliotransmitter
  • Glutamate
  • Glycine
  • L-serine
  • NMDA receptor
  • Neurodegeneration
  • Neurotoxicity
  • Neurotransmission
  • Schizophrenia
  • Serine racemase

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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