Glycogen synthase kinase-3 (GSK3) in psychiatric disease and therapeutic interventions

Richard S Jope, Myoung Sun Roh

Research output: Contribution to journalArticle

254 Citations (Scopus)

Abstract

Glycogen synthase kinase-3 (GSK3) has recently been linked to mood disorders and schizophrenia, and the neurotransmitter systems and therapeutic treatments associated with these diseases. GSK3 is a widely influential enzyme that is capable of phosphorylating, and thereby regulating, over forty known substrates. Four mechanisms regulating GSK3 (phosphorylation, protein complexes, localization, and substrate phosphorylation) combine to provide substrate-specific regulation of the actions of GSK3. Several intracellular signaling cascades converge on GSK3 to modulate its activity, and several neurotransmitter systems also regulate GSK3, including serotonergic, dopaminergic, cholinergic, and glutamatergic systems. Because of changes in these neurotransmitter systems and the actions of therapeutic drugs, GSK3 has been linked to the mood disorders, bipolar disorder and depression, and to schizophrenia. Inhibition of GSK3 may be an important therapeutic target of mood stabilizers, and regulation of GSK3 may be involved in the therapeutic effects of other drugs used in psychiatry. Dysregulated GSK3 in bipolar disorder, depression, and schizophrenia could have multiple effects that could impair neural plasticity, such as modulation of neuronal architecture, neurogenesis, gene expression, and the ability of neurons to respond to stressful, potentially lethal, conditions. In part because of these key actions of GSK3 and its associations with mood disorders and schizophrenia, much research is currently being devoted to identifying new selective inhibitors of GSK3.

Original languageEnglish
Pages (from-to)1421-1434
Number of pages14
JournalCurrent Drug Targets
Volume7
Issue number11
StatePublished - Nov 1 2006
Externally publishedYes

Fingerprint

Glycogen Synthase Kinase 3
Psychiatry
Bipolar Disorder
Schizophrenia
Therapeutics
Mood Disorders
Neurotransmitter Agents
Phosphorylation
Substrates
Neuronal Plasticity
Aptitude
Neurogenesis
Therapeutic Uses
Gene expression
Pharmaceutical Preparations
Cholinergic Agents
Neurons
Plasticity

Keywords

  • Akt
  • Bipolar disorder
  • Depression
  • Dopamine
  • GSK3
  • Schizophrenia
  • Serotonin

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmaceutical Science

Cite this

Glycogen synthase kinase-3 (GSK3) in psychiatric disease and therapeutic interventions. / Jope, Richard S; Roh, Myoung Sun.

In: Current Drug Targets, Vol. 7, No. 11, 01.11.2006, p. 1421-1434.

Research output: Contribution to journalArticle

@article{57a26a989af64112a115e3df2d072679,
title = "Glycogen synthase kinase-3 (GSK3) in psychiatric disease and therapeutic interventions",
abstract = "Glycogen synthase kinase-3 (GSK3) has recently been linked to mood disorders and schizophrenia, and the neurotransmitter systems and therapeutic treatments associated with these diseases. GSK3 is a widely influential enzyme that is capable of phosphorylating, and thereby regulating, over forty known substrates. Four mechanisms regulating GSK3 (phosphorylation, protein complexes, localization, and substrate phosphorylation) combine to provide substrate-specific regulation of the actions of GSK3. Several intracellular signaling cascades converge on GSK3 to modulate its activity, and several neurotransmitter systems also regulate GSK3, including serotonergic, dopaminergic, cholinergic, and glutamatergic systems. Because of changes in these neurotransmitter systems and the actions of therapeutic drugs, GSK3 has been linked to the mood disorders, bipolar disorder and depression, and to schizophrenia. Inhibition of GSK3 may be an important therapeutic target of mood stabilizers, and regulation of GSK3 may be involved in the therapeutic effects of other drugs used in psychiatry. Dysregulated GSK3 in bipolar disorder, depression, and schizophrenia could have multiple effects that could impair neural plasticity, such as modulation of neuronal architecture, neurogenesis, gene expression, and the ability of neurons to respond to stressful, potentially lethal, conditions. In part because of these key actions of GSK3 and its associations with mood disorders and schizophrenia, much research is currently being devoted to identifying new selective inhibitors of GSK3.",
keywords = "Akt, Bipolar disorder, Depression, Dopamine, GSK3, Schizophrenia, Serotonin",
author = "Jope, {Richard S} and Roh, {Myoung Sun}",
year = "2006",
month = "11",
day = "1",
language = "English",
volume = "7",
pages = "1421--1434",
journal = "Current Drug Targets",
issn = "1389-4501",
publisher = "Bentham Science Publishers B.V.",
number = "11",

}

TY - JOUR

T1 - Glycogen synthase kinase-3 (GSK3) in psychiatric disease and therapeutic interventions

AU - Jope, Richard S

AU - Roh, Myoung Sun

PY - 2006/11/1

Y1 - 2006/11/1

N2 - Glycogen synthase kinase-3 (GSK3) has recently been linked to mood disorders and schizophrenia, and the neurotransmitter systems and therapeutic treatments associated with these diseases. GSK3 is a widely influential enzyme that is capable of phosphorylating, and thereby regulating, over forty known substrates. Four mechanisms regulating GSK3 (phosphorylation, protein complexes, localization, and substrate phosphorylation) combine to provide substrate-specific regulation of the actions of GSK3. Several intracellular signaling cascades converge on GSK3 to modulate its activity, and several neurotransmitter systems also regulate GSK3, including serotonergic, dopaminergic, cholinergic, and glutamatergic systems. Because of changes in these neurotransmitter systems and the actions of therapeutic drugs, GSK3 has been linked to the mood disorders, bipolar disorder and depression, and to schizophrenia. Inhibition of GSK3 may be an important therapeutic target of mood stabilizers, and regulation of GSK3 may be involved in the therapeutic effects of other drugs used in psychiatry. Dysregulated GSK3 in bipolar disorder, depression, and schizophrenia could have multiple effects that could impair neural plasticity, such as modulation of neuronal architecture, neurogenesis, gene expression, and the ability of neurons to respond to stressful, potentially lethal, conditions. In part because of these key actions of GSK3 and its associations with mood disorders and schizophrenia, much research is currently being devoted to identifying new selective inhibitors of GSK3.

AB - Glycogen synthase kinase-3 (GSK3) has recently been linked to mood disorders and schizophrenia, and the neurotransmitter systems and therapeutic treatments associated with these diseases. GSK3 is a widely influential enzyme that is capable of phosphorylating, and thereby regulating, over forty known substrates. Four mechanisms regulating GSK3 (phosphorylation, protein complexes, localization, and substrate phosphorylation) combine to provide substrate-specific regulation of the actions of GSK3. Several intracellular signaling cascades converge on GSK3 to modulate its activity, and several neurotransmitter systems also regulate GSK3, including serotonergic, dopaminergic, cholinergic, and glutamatergic systems. Because of changes in these neurotransmitter systems and the actions of therapeutic drugs, GSK3 has been linked to the mood disorders, bipolar disorder and depression, and to schizophrenia. Inhibition of GSK3 may be an important therapeutic target of mood stabilizers, and regulation of GSK3 may be involved in the therapeutic effects of other drugs used in psychiatry. Dysregulated GSK3 in bipolar disorder, depression, and schizophrenia could have multiple effects that could impair neural plasticity, such as modulation of neuronal architecture, neurogenesis, gene expression, and the ability of neurons to respond to stressful, potentially lethal, conditions. In part because of these key actions of GSK3 and its associations with mood disorders and schizophrenia, much research is currently being devoted to identifying new selective inhibitors of GSK3.

KW - Akt

KW - Bipolar disorder

KW - Depression

KW - Dopamine

KW - GSK3

KW - Schizophrenia

KW - Serotonin

UR - http://www.scopus.com/inward/record.url?scp=33750866196&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33750866196&partnerID=8YFLogxK

M3 - Article

C2 - 17100582

AN - SCOPUS:33750866196

VL - 7

SP - 1421

EP - 1434

JO - Current Drug Targets

JF - Current Drug Targets

SN - 1389-4501

IS - 11

ER -