Identification of NEK3 and MOK as novel targets for lithium

Abstract

Lithium ion, commonly used as the carbonate salt in the treatment of bipolar disorders, has been identified as an inhibitor of several kinases, including Glycogen Synthase Kinase-3β, for almost 20 years. However, both the exact mechanism of enzymatic inhibition and its apparent specificity for certain metalloenzymes are still a matter of debate. A data-driven hypothesis is presented that accounts for the specificity profile of kinase inhibition by lithium in terms of the presence of a unique protein environment in the magnesium-binding site. This hypothesis has been validated by the discovery of two novel potential targets for lithium, namely NEK3 and MOK, which are related to neuronal function.