An emerging role for Wnt and GSK3 signaling pathways in schizophrenia

Clin Genet. 2013 Jun;83(6):511-7. doi: 10.1111/cge.12111. Epub 2013 Apr 1.

Abstract

Schizophrenia is a disabling illness with limited treatment options. The underlying pathophysiology remains unknown, partially due to its heterogeneous nature, and a lack of understanding of the biological functions of genetic risk factors. Several signaling pathways have been implicated, however, with the varying degrees of support. In this article, I will focus on the converging evidence supporting a prominent role for Wnt and glycogen synthase kinase 3 (GSK3) signaling in the biological bases of schizophrenia. This includes current pharmacological therapies that target GSK3, animal model and cell-based studies, and recent human genetic findings that implicate Wnt and GSK3 signaling.

MeSH terms

  • Animals
  • Antipsychotic Agents / therapeutic use
  • DNA Copy Number Variations
  • Glycogen Synthase Kinase 3 / genetics*
  • Glycogen Synthase Kinase 3 / metabolism
  • Humans
  • Models, Genetic
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism
  • Receptors, Dopamine / genetics
  • Receptors, Dopamine / metabolism
  • Schizophrenia / drug therapy
  • Schizophrenia / genetics*
  • Schizophrenia / physiopathology
  • Signal Transduction / drug effects
  • Signal Transduction / genetics*
  • Signal Transduction / physiology
  • Wnt Signaling Pathway / drug effects
  • Wnt Signaling Pathway / genetics
  • Wnt Signaling Pathway / physiology
  • Wnt1 Protein / genetics*
  • Wnt1 Protein / metabolism
  • beta Catenin / genetics
  • beta Catenin / metabolism

Substances

  • Antipsychotic Agents
  • DISC1 protein, human
  • Nerve Tissue Proteins
  • Receptors, Dopamine
  • Wnt1 Protein
  • beta Catenin
  • Proto-Oncogene Proteins c-akt
  • Glycogen Synthase Kinase 3