D-
Serine is a potent co-agonist at the
NMDA glutamate receptor and has been the object of many preclinical studies to ascertain the nature of its metabolism, its regional and cellular distribution in the brain, its physiological functions and its possible clinical relevance. The
enzymes involved in its formation and catabolism are
serine racemase (SR) and
D-amino acid oxidase (DAAO), respectively, and manipulations of the activity of those
enzymes have been useful in developing animal models of
schizophrenia and in providing clues to the development of potential new
antipsychotic strategies. Clinical studies have been conducted in
schizophrenia patients to evaluate body fluid levels of D-
serine and/or to use D-
serine alone or in combination with
antipsychotics to determine its effectiveness as a therapeutic agent. D-
serine has also been used in combination with DAAO inhibitors in preclinical investigations, and interesting results have been obtained. Genetic studies and postmortem brain studies have also been conducted on D-
serine and the
enzymes involved in its metabolism. It is also of considerable interest that in recent years clinical and preclinical investigations have suggested that D-
serine may also have
antidepressant properties. Clinical studies have also shown that D-
serine may be a
biomarker for
antidepressant response to
ketamine. Relevant to both
schizophrenia and depression, preclinical and clinical studies with D-
serine indicate that it may be effective in reducing
cognitive dysfunction.