Fig. 7.

Lithium’s mechanism of action as it relates to glycogen synthase kinase (GSK)-3β. Lithium has the ability to both directly and indirectly inhibit GSK-3β activity, making it an appealing therapeutic strategy to stimulate Wnt/β-catenin signaling. Direct inhibition occurs via competition with Mg²⁺ at the GSK-3β active site. Indirect inhibition occurs via serine 9 phosphorylation at the GSK-3β N-terminus. cAMP = cyclic adenosine monophosphate, PKA = protein kinase A, P = phosphorylation site, PI3K = phosphatidylinositol 3-kinase, PKB = protein kinase B, and PKC = protein kinase C.