In this study, we carried out a comprehensive analysis of the association of the rs3755557 polymorphism within GSK3B and schizophrenia in Han Chinese individuals.
Taken into account that increased Glycogen Synthase Kinase 3 Beta (GSK-3β) activity is associated with schizophrenia pathophysiology and certain antipsychotics can be able to decrease GSK3β activity, inhibition of GSK-3β activity could be a novel approach for the treatment of schizophrenia.
Taken into account that increased Glycogen Synthase Kinase 3 Beta (GSK-3β) activity is associated with schizophrenia pathophysiology and certain antipsychotics can be able to decrease GSK3β activity, inhibition of GSK-3β activity could be a novel approach for the treatment of schizophrenia.
The implication of this finding for the biology of psychoses warrants further studies to clarify whether increased GSK3B may be useful as a biomarker for psychosis in general, and schizophrenia in particular.
Glycogen synthase kinase 3β (GSK3β) is a highly conserved serine/threonine kinase that has been implicated in both psychiatric and neurodegenerative diseases including schizophrenia, bipolar disorder, and Alzheimer's disease; therefore regulating its activity has become an important strategy for treatment of cognitive impairments in these disorders.
The single nucleotide polymorphism (SNP) rs334558 on the glycogen synthase kinase-3β (GSK3β) gene has been identified as a genetic risk loci associated with schizophrenia and bipolar disorder.
GSK-3β Interacts with Dopamine D1 Receptor to Regulate Receptor Function: Implication for Prefrontal Cortical D1 Receptor Dysfunction in Schizophrenia.
Our results point to the polymorphisms of DCC and GSK3β as contributors to the genetic basis of individual differences in the susceptibility to schizophrenia.
Our results provide evidence that the GSK3B gene could be a promising region which contains genetic risk for both major depressive disorder and schizophrenia in the Han Chinese population.
These studies show region-specific abnormalities of both protein and mRNA expression of GSK-3β and β-catenin in postmortem brains of subjects with BP but not subjects with SZ.
Here, by using meta-analysis we reported that glycogen synthase kinase 3β promoter inactive mutant rs334558 may contribute to the development of schizophrenia not bipolar disorder.
Since Wnt signaling is important in organizing the developing brain, it is reasonable to propose that defects in Wnt signaling could contribute to Schizophrenia, particularly since the neuro-developmental hypothesis of the disease implies subtle dys-regulation of brain development, including some core components of the Wnt signaling pathways such as GSK-3β or Disrupted in Schizophrenia-1 (DISC-1).
By using the Molecular Genetics of Schizophrenia data set, we were able to test and confirm that markers in NRXN1 and GSK3B have epistatic interactions in human populations that can jointly modulate risk of schizophrenia.
The findings suggest that seemingly disparate candidate genes for SZ and BD can be incorporated into a common molecular network revolving around GSK3β/β-catenin signaling.
In conclusion, these results suggest that the GSK-3 beta is not associated with the development of schizophrenia and bipolar disorder in Korean population.