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?
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.
Mothet
J P
JP
Laboratoire de neurobiologie cellulaire et moléculaire du CNRS, institut fédératif de neurobiologie Alfred Fessard, 1, avenue de la Terrasse, 91198 Gif-sur-Yvette, France. mothet@nbcm.cnrs-gif.fr
D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D001923:Brain Chemistry; D018698:Glutamic Acid / Q000502:physiology*; D006801:Humans; D016202:N-Methylaspartate / Q000494:pharmacology; D019636:Neurodegenerative Diseases / Q000628:therapy*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D012694:Serine / Q000032:analysis* / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology
D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D012694:Serine; D016202:N-Methylaspartate