Identification of NEK3 and MOK as novel targets for lithium

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 certa...

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Bibliographic Details
Published in:Chemical biology & drug design 2019-05, Vol.93 (5), p.965-969
Main Authors: Bravo, Ana, Lucio, Héctor, Sánchez‐Murcia, Pedro A., Jiménez‐Ruiz, Antonio, Petrone, Paula M., Gago, Federico, Cortés Cabrera, Alvaro
Format: Article
Language:English
Subjects:
Antigens, Neoplasm - chemistry
Antigens, Neoplasm - metabolism
axonal growth
Binding Sites
bipolar disorder
Glycogen Synthase Kinase 3 beta - chemistry
Glycogen Synthase Kinase 3 beta - metabolism
GSK3B
Humans
Inhibitory Concentration 50
Ions - chemistry
lithium
Lithium - chemistry
Lithium - metabolism
Magnesium - chemistry
Magnesium - metabolism
Mitogen-Activated Protein Kinases - chemistry
Mitogen-Activated Protein Kinases - metabolism
MOK
Molecular Dynamics Simulation
NEK3
NIMA-Related Kinases - chemistry
NIMA-Related Kinases - metabolism
Protein Structure, Tertiary
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Summary: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. 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.
ISSN:1747-0277
1747-0285
DOI:10.1111/cbdd.13487