Roles of the Akt/GSK-3 and Wnt signaling pathways in schizophrenia and antipsychotic drug action.
Dopamine D(2) receptor antagonism is a unifying property of all antipsychotic drugs in clinical use. Remarkably, the effector molecules through which these medications exert their actions remain poorly characterized. Increasing attention is being focused on Akt/glycogen synthase kinase-3 (GSK-3) and wingless (Wnt) signaling pathways, which have been associated with schizophrenia in a number of genetic and postmortem studies. Antipsychotic medications may treat symptoms of psychosis, at least in part, through modulation of levels and activity of Akt, GSK-3, and Wnt-related intracellular signaling. The authors review evidence that Akt/GSK-3 and Wnt-related pathways are involved in the pathogenesis of schizophrenia as well as details of intracellular events related to these molecules mediated by both typical and atypical antipsychotic medications. Further study of Akt/GSK-3 and Wnt signaling may ultimately lead to alternative therapeutics of schizophrenia-related disorders.
Freyberg
Zachary
Z
Department of Psychiatry, Center for Molecular Recognition, College of Physicians and Surgeons, Columbia University, NY 10032, USA. zf2101@columbia.edu
Ferrando
Stephen J
SJ
Javitch
Jonathan A
JA
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014150:Antipsychotic Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D019390:Arrestins / Q000037:antagonists & inhibitors; D038362:Glycogen Synthase Kinase 3 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D020033:Protein Isoforms; D012559:Schizophrenia / Q000188:drug therapy* / Q000235:genetics*; D015398:Signal Transduction / Q000187:drug effects*; D051153:Wnt Proteins / Q000235:genetics*; D051176:beta Catenin / Q000037:antagonists & inhibitors
C486377:AKTIP protein, human; D048868:Adaptor Proteins, Signal Transducing; D014150:Antipsychotic Agents; D051017:Apoptosis Regulatory Proteins; D019390:Arrestins; C495270:CTNNB1 protein, human; D020033:Protein Isoforms; D051153:Wnt Proteins; D051176:beta Catenin; D038362:Glycogen Synthase Kinase 3