GSK3β: A Master Player in Depressive Disorder Pathogenesis and Treatment Responsiveness

Glycogen synthase kinase 3 beta (GSK3 beta), originally described as a negative regulator of glycogen synthesis, is a molecular hub linking numerous signaling pathways in a cell. Specific GSK3 beta inhibitors have anti-depressant effects and reduce depressive-like behavior in animal models of depression. Therefore, GSK3 beta is suggested to be engaged in the pathogenesis of major depressive disorder, and to be a target and/or modifier of anti-depressants' action. In this review, we discuss abnormalities in the activity of GSK3 beta and its upstream regulators in different brain regions during depressive episodes. Additionally, putative role(s) of GSK3 beta in the pathogenesis of depression and the influence of anti-depressants on GSK3 beta activity are discussed.