Inhibition of glycogen synthase kinase-3

A potential therapeutic target of lithium

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Glycogen synthase kinase-3 (GSK3) is inhibited by the mood stabilizer lithium in two ways. First, lithium directly inhibits the enzyme. This direct inhibitory effect is amplified in vivo by an increase in the inhibitory phosphorylation of an N-terminal serine in GSK3, enabling low concentrations of lithium to significantly modulate GSK3. Inhibition of GSK3 by lithium has multiple effects on cellular functions due to the numerous substrates of GSK3, any of which may contribute to the mood stabilizing action of lithium. These include regulation of neural plasticity through changes in cellular architecture and remodelling events, regulation of gene expression through modulation of the activities of transcription factors, and regulation of cellular responses to stress and the ensuing modulation of cell survival. The manifold influences of GSK3 on the dynamics of neuronal function provide substantial support for the proposal that GSK3 may be a key target for the therapeutic actions of lithium.

Original languageEnglish
Pages (from-to)171-179
Number of pages9
JournalClinical Neuroscience Research
Volume4
Issue number3-4 SPEC. ISS.
DOIs
StatePublished - Dec 1 2004
Externally publishedYes

Fingerprint

Glycogen Synthase Kinase 3
Lithium
Therapeutics
Neuronal Plasticity
Gene Expression Regulation
Inhibition (Psychology)
Serine
Cell Survival
Transcription Factors
Phosphorylation
Enzymes

Keywords

  • Apoptosis
  • Glycogen synthase kinase-3
  • Lithium
  • Mood stabilizers

ASJC Scopus subject areas

  • Clinical Neurology
  • Psychiatry and Mental health
  • Biological Psychiatry
  • Neurology
  • Neuropsychology and Physiological Psychology

Cite this

Inhibition of glycogen synthase kinase-3 : A potential therapeutic target of lithium. / Jope, Richard S.

In: Clinical Neuroscience Research, Vol. 4, No. 3-4 SPEC. ISS., 01.12.2004, p. 171-179.

Research output: Contribution to journalArticle

@article{007aa76f94eb4021b9c0d2ff0c52ebfa,
title = "Inhibition of glycogen synthase kinase-3: A potential therapeutic target of lithium",
abstract = "Glycogen synthase kinase-3 (GSK3) is inhibited by the mood stabilizer lithium in two ways. First, lithium directly inhibits the enzyme. This direct inhibitory effect is amplified in vivo by an increase in the inhibitory phosphorylation of an N-terminal serine in GSK3, enabling low concentrations of lithium to significantly modulate GSK3. Inhibition of GSK3 by lithium has multiple effects on cellular functions due to the numerous substrates of GSK3, any of which may contribute to the mood stabilizing action of lithium. These include regulation of neural plasticity through changes in cellular architecture and remodelling events, regulation of gene expression through modulation of the activities of transcription factors, and regulation of cellular responses to stress and the ensuing modulation of cell survival. The manifold influences of GSK3 on the dynamics of neuronal function provide substantial support for the proposal that GSK3 may be a key target for the therapeutic actions of lithium.",
keywords = "Apoptosis, Glycogen synthase kinase-3, Lithium, Mood stabilizers",
author = "Jope, {Richard S}",
year = "2004",
month = "12",
day = "1",
doi = "10.1016/j.cnr.2004.09.009",
language = "English",
volume = "4",
pages = "171--179",
journal = "Clinical Neuroscience Research",
issn = "1566-2772",
publisher = "Elsevier BV",
number = "3-4 SPEC. ISS.",

}

TY - JOUR

T1 - Inhibition of glycogen synthase kinase-3

T2 - A potential therapeutic target of lithium

AU - Jope, Richard S

PY - 2004/12/1

Y1 - 2004/12/1

N2 - Glycogen synthase kinase-3 (GSK3) is inhibited by the mood stabilizer lithium in two ways. First, lithium directly inhibits the enzyme. This direct inhibitory effect is amplified in vivo by an increase in the inhibitory phosphorylation of an N-terminal serine in GSK3, enabling low concentrations of lithium to significantly modulate GSK3. Inhibition of GSK3 by lithium has multiple effects on cellular functions due to the numerous substrates of GSK3, any of which may contribute to the mood stabilizing action of lithium. These include regulation of neural plasticity through changes in cellular architecture and remodelling events, regulation of gene expression through modulation of the activities of transcription factors, and regulation of cellular responses to stress and the ensuing modulation of cell survival. The manifold influences of GSK3 on the dynamics of neuronal function provide substantial support for the proposal that GSK3 may be a key target for the therapeutic actions of lithium.

AB - Glycogen synthase kinase-3 (GSK3) is inhibited by the mood stabilizer lithium in two ways. First, lithium directly inhibits the enzyme. This direct inhibitory effect is amplified in vivo by an increase in the inhibitory phosphorylation of an N-terminal serine in GSK3, enabling low concentrations of lithium to significantly modulate GSK3. Inhibition of GSK3 by lithium has multiple effects on cellular functions due to the numerous substrates of GSK3, any of which may contribute to the mood stabilizing action of lithium. These include regulation of neural plasticity through changes in cellular architecture and remodelling events, regulation of gene expression through modulation of the activities of transcription factors, and regulation of cellular responses to stress and the ensuing modulation of cell survival. The manifold influences of GSK3 on the dynamics of neuronal function provide substantial support for the proposal that GSK3 may be a key target for the therapeutic actions of lithium.

KW - Apoptosis

KW - Glycogen synthase kinase-3

KW - Lithium

KW - Mood stabilizers

UR - http://www.scopus.com/inward/record.url?scp=13344270362&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=13344270362&partnerID=8YFLogxK

U2 - 10.1016/j.cnr.2004.09.009

DO - 10.1016/j.cnr.2004.09.009

M3 - Article

VL - 4

SP - 171

EP - 179

JO - Clinical Neuroscience Research

JF - Clinical Neuroscience Research

SN - 1566-2772

IS - 3-4 SPEC. ISS.

ER -