The role of phospholipases A2 in schizophrenia.
A range of neurotransmitter systems have been implicated in the pathogenesis of schizophrenia based on the antidopaminergic activities of antipsychotic medications, and chemicals that can induce psychotic-like symptoms, such as ketamine or PCP. Such neurotransmitter systems often mediate their cellular response via G-protein-coupled release of arachidonic acid (AA) via the activation of phospholipases A2 (PLA2s). The interaction of three PLA2s are important for the regulation of the release of AA--phospholipase A2 Group 2 A, phospholipase A2 Group 4A and phospholipase A2 Group 6A. Gene variations of these three key enzymes have been associated with schizophrenia with conflicting results. Preclinical data suggest that the activity of these three enzymes are associated with monoaminergic neurotransmission, and may contribute to the differential efficacy of antipsychotic medications, as well as other biological changes thought to underlie schizophrenia, such as altered neurodevelopment and synaptic remodelling. We review the evidence and discuss the potential roles of these three key enzymes for schizophrenia with particular emphasis on published association studies.
Law
M H
MH
Genomic Disorders Research Centre, Melbourne, VI, Australia.
Cotton
R G H
RG
Berger
G E
GE
D014150:Antipsychotic Agents / Q000494:pharmacology / Q000627:therapeutic use; D016718:Arachidonic Acid / Q000378:metabolism; D006801:Humans; D009525:Niacin / Q000378:metabolism*; D010741:Phospholipases A / Q000145:classification / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D054467:Phospholipases A2; D012559:Schizophrenia / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics
D014150:Antipsychotic Agents; D009525:Niacin; D016718:Arachidonic Acid; D010741:Phospholipases A; D054467:Phospholipases A2