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 language | English |
|---|---|
| Pages (from-to) | 171-179 |
| Number of pages | 9 |
| Journal | Clinical Neuroscience Research |
| Volume | 4 |
| Issue number | 3-4 SPEC. ISS. |
| DOIs | |
| State | Published - Dec 1 2004 |
| Externally published | Yes |
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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 journal › Article
}
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 -