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

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