D-Amino acids in brain neurotransmission and synaptic plasticity

Amino Acids. 2012 Nov;43(5):1851-60. doi: 10.1007/s00726-012-1346-3. Epub 2012 Aug 11.


Far from our initial view of D-amino acids as being limited to invertebrates, they are now considered active molecules at synapses of mammalian central and peripheral nervous systems, capable of modulating synaptic communication within neuronal networks. In particular, experimental data accumulated in the last few decades show that through the regulation of glutamatergic neurotransmission, D-serine influences the functional plasticity of cerebral circuitry throughout life. In addition, the modulation of NMDA-R-dependent signalling by D-aspartate has been demonstrated by pharmacological studies and after the targeted deletion of the D-aspartate-degrading enzyme. Considering the major contribution of the glutamatergic system to a wide range of neurological disorders such as schizophrenia, Alzheimer's disease and amyotrophic lateral sclerosis, an improved understanding of the mechanisms of D-amino-acid-dependent neuromodulation will certainly offer new insights for the development of relevant strategies to treat these neurological diseases.

Publication types

  • Review

MeSH terms

  • Animals
  • Brain / metabolism*
  • Brain / physiopathology
  • D-Amino-Acid Oxidase / metabolism
  • D-Aspartic Acid / metabolism
  • Humans
  • Nervous System Diseases / metabolism*
  • Nervous System Diseases / physiopathology
  • Neuronal Plasticity / physiology*
  • Neurons / metabolism
  • Neurotransmitter Agents / metabolism
  • Racemases and Epimerases / metabolism
  • Receptors, N-Methyl-D-Aspartate / metabolism*
  • Serine / metabolism
  • Stereoisomerism
  • Synapses / metabolism*
  • Synaptic Transmission / physiology*


  • Neurotransmitter Agents
  • Receptors, N-Methyl-D-Aspartate
  • Serine
  • D-Aspartic Acid
  • DAO protein, human
  • D-Amino-Acid Oxidase
  • Racemases and Epimerases
  • serine racemase