The effects of clozapine on the GSK-3-mediated signaling pathway

We investigated the effect of 10 μM clozapine on the activity of glycogen synthase kinase-3β (GSK-3β) and its upstream and downstream molecules in SH-SY5Y human neuroblastoma cells. Clozapine activates both Akt- and Dvl-mediated phosphorylation of GSK-3β through phosphorylation at Ser9, and increased total cellular and intranuclear levels of β-catenin. Pretreatment with the specific inhibitor of the phosphatidylinositol 3-kinase (PI3K)-Akt pathway, LY294002 (20 μM), prevented the phosphorylation of Akt but did not affect the phosphorylation of GSK-3β. These results suggest that clozapine regulates the phosphorylation of GSK-3β through Wnt signal pathways involving Dvl upstream but not through the PI3K-Akt pathway in SH-SY5Y cells.