Reviewing the role of the genes G72 and DAAO in glutamate neurotransmission in schizophrenia.
We review the role of two susceptibility genes; G72 and DAAO in glutamate neurotransmission and the aetiology of schizophrenia. The gene product of G72 is an activator of DAAO (D-amino acid oxidase), which is the only enzyme oxidising D-serine. D-serine is an important co-agonist for the NMDA glutamate receptor and plays a role in neuronal migration and cell death. Studies of D-serine revealed lower serum levels in schizophrenia patients as compared to healthy controls. Furthermore, administration of D-serine as add-on medication reduced the symptoms of schizophrenia. The underlying mechanism of the involvement of G72 and DAAO in schizophrenia is probably based on decreased levels of D-serine and decreased NMDA receptor functioning in patients. The involvement of this gene is therefore indirect support for the glutamate dysfunction hypothesis in schizophrenia.
Boks
M P M
MP
Department of Psychiatry, B01.206, University Medical Centre Utrecht, PO Box 85500, 3508 GA Utrecht, The Netherlands. mboks@umcutrecht.nl
Rietkerk
T
T
van de Beek
M H
MH
Sommer
I E
IE
de Koning
T J
TJ
Kahn
R S
RS
D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D003605:D-Amino-Acid Oxidase / Q000235:genetics / Q000502:physiology*; D020022:Genetic Predisposition to Disease; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008954:Models, Biological; D012559:Schizophrenia / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D009435:Synaptic Transmission / Q000235:genetics*
D002352:Carrier Proteins; C475071:DAOA protein, human; D047908:Intracellular Signaling Peptides and Proteins; D018698:Glutamic Acid; D003605:D-Amino-Acid Oxidase