Lithium and GSK-3: one inhibitor, two inhibitory actions, multiple outcomes

The intrigue of lithium, the simplest drug in the modern pharmacopoeia, extends from its complex actions in cells to its therapeutic effects as a mood stabilizer. New surprises from studies of glycogen synthase kinase 3 (GSK-3) show that lithium reduces GSK-3 activity in two ways, both directly and by increasing the inhibitory phosphorylation of GSK-3. These dual effects can act in concert to magnify the influence of lithium on crucial GSK-3-regulated functions (gene expression, cell structure and survival).