Physiological relevance of endogenous free D-serine in the mammalian brain: are scientists on a royal road for the treatment of glutamatergic-related brain disorders?

Pathol Biol (Paris). 2001 Oct;49(8):655-9. doi: 10.1016/s0369-8114(01)00227-9.


Over the last century, it has been considered that amino acids in mammalian tissues and body fluids occur solely in the L-configuration whether free or as components of peptides and proteins. However, the recent discovery that high levels of D-serine and D-aspartate are present in Mammals overturns this long-cherished theory. In this review, we focus on recent findings regarding the physiological relevance of D-serine, a new neurotransmitter formed in glial cells, that serves as the endogenous ligand for the accessory strychnine-insensitive glycine site of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptors. This unusual molecule not only questions our basic ideas about how nerve cells converse but also offers a novel way to treat some brain disorders as both over-stimulation and down regulation of NMDA receptors has been implicated in a large number of acute and chronic degenerative conditions.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Astrocytes / metabolism
  • Brain Chemistry*
  • Glutamic Acid / physiology*
  • Humans
  • N-Methylaspartate / pharmacology
  • Neurodegenerative Diseases / therapy*
  • Receptors, N-Methyl-D-Aspartate / metabolism
  • Serine / analysis*
  • Serine / physiology*
  • Synaptic Transmission / physiology


  • Receptors, N-Methyl-D-Aspartate
  • Glutamic Acid
  • Serine
  • N-Methylaspartate