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Identification of NEK3 and MOK as novel targets for lithium

Ana Bravo1,2, Héctor de Lucio2, Pedro A Sánchez-Murcia1

  • 1Área de Farmacología, Departamento de Ciencias Biomédicas, Unidad Asociada al IQM-CSIC, Universidad de Alcalá, Alcalá de Henares, Spain.

Chemical Biology & Drug Design
|January 23, 2019
PubMed

Insights

Lithium ions inhibit kinases by interacting with the magnesium-binding site. This study identifies novel lithium targets, NEK3 and MOK, potentially impacting neuronal function and bipolar disorder treatments.

Area of Science:

  • Biochemistry
  • Neuropharmacology
  • Enzymology

Background:

  • Lithium carbonate is a standard treatment for bipolar disorders.
  • Lithium ion is known to inhibit various kinases, notably Glycogen Synthase Kinase-3β (GSK-3β), for two decades.
  • The precise mechanism and specificity of lithium's kinase inhibition remain incompletely understood.

Discussion:

  • A novel hypothesis proposes lithium's kinase inhibition specificity arises from unique protein environments in magnesium-binding sites.
  • This data-driven hypothesis offers a mechanistic explanation for observed inhibition patterns.
  • The hypothesis addresses the long-standing questions regarding lithium's enzyme interactions.

Key Insights:

  • Lithium's specificity for certain metalloenzymes is explained by unique magnesium-binding site protein environments.
  • NEK3 and MOK kinases are identified as novel potential targets for lithium.
  • These targets are implicated in neuronal function, suggesting new therapeutic avenues.

Outlook:

  • Further research can explore the therapeutic potential of targeting NEK3 and MOK with lithium.
  • This work may lead to the development of more specific lithium-based therapeutics.
  • Investigating lithium's interaction with other metalloenzymes could reveal additional targets.
Keywords:
GSK3BMOKNEK3axonal growthbipolar disorderlithium

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