Abstract
Glycogen synthase kinase-3β (GSK3β) is a central figure in many intracellular signaling systems and is directly regulated by lithium. Substantial evidence now indicates that an important property of the mood stabilizer, lithium, is to influence GSK3β-linked signaling pathways. This raises the possibility that other mood stabilizers act in a similar manner, which may include modulation of signaling systems leading to GSK3β, direct regulation of GSK3β or regulation of signaling intermediates downstream of GSK3β. Downstream targets of GSK3β, and thus potential targets of mood stabilizers, are several key transcription factors, including β-catenin, AP-1, cyclic AMP-response element binding protein, NFκB, Myc, heat shock factor-1, nuclear factor of activated T-cells and CCAAT/enhancer-binding proteins. GSK3β also is an important modulator of cell death, which may be a consequence of its regulatory effects on transcription factor activities. GSK3β facilitates apoptosis, and lithium's inhibition of GSK3β supports cell survival. Thus, signaling systems determining cell fate appear to be important targets of mood stabilizers, and these may include signaling pathways encompassing GSK3β, including transcription factors regulated by GSK3β.
| Original language | English |
|---|---|
| Journal | Molecular Psychiatry |
| Volume | 7 |
| Issue number | SUPPL. 1 |
| DOIs | |
| State | Published - Apr 16 2002 |
| Externally published | Yes |
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Keywords
- β-catenin
- Apoptosis
- Bipolar disorder
- CREB
- Lithium
- Neuroprotection
ASJC Scopus subject areas
- Molecular Biology
- Psychiatry and Mental health
Cite this
Mood stabilizers, glycogen synthase kinase-3β and cell survival. / Jope, Richard S; Bijur, G. N.
In: Molecular Psychiatry, Vol. 7, No. SUPPL. 1, 16.04.2002.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Mood stabilizers, glycogen synthase kinase-3β and cell survival
AU - Jope, Richard S
AU - Bijur, G. N.
PY - 2002/4/16
Y1 - 2002/4/16
N2 - Glycogen synthase kinase-3β (GSK3β) is a central figure in many intracellular signaling systems and is directly regulated by lithium. Substantial evidence now indicates that an important property of the mood stabilizer, lithium, is to influence GSK3β-linked signaling pathways. This raises the possibility that other mood stabilizers act in a similar manner, which may include modulation of signaling systems leading to GSK3β, direct regulation of GSK3β or regulation of signaling intermediates downstream of GSK3β. Downstream targets of GSK3β, and thus potential targets of mood stabilizers, are several key transcription factors, including β-catenin, AP-1, cyclic AMP-response element binding protein, NFκB, Myc, heat shock factor-1, nuclear factor of activated T-cells and CCAAT/enhancer-binding proteins. GSK3β also is an important modulator of cell death, which may be a consequence of its regulatory effects on transcription factor activities. GSK3β facilitates apoptosis, and lithium's inhibition of GSK3β supports cell survival. Thus, signaling systems determining cell fate appear to be important targets of mood stabilizers, and these may include signaling pathways encompassing GSK3β, including transcription factors regulated by GSK3β.
AB - Glycogen synthase kinase-3β (GSK3β) is a central figure in many intracellular signaling systems and is directly regulated by lithium. Substantial evidence now indicates that an important property of the mood stabilizer, lithium, is to influence GSK3β-linked signaling pathways. This raises the possibility that other mood stabilizers act in a similar manner, which may include modulation of signaling systems leading to GSK3β, direct regulation of GSK3β or regulation of signaling intermediates downstream of GSK3β. Downstream targets of GSK3β, and thus potential targets of mood stabilizers, are several key transcription factors, including β-catenin, AP-1, cyclic AMP-response element binding protein, NFκB, Myc, heat shock factor-1, nuclear factor of activated T-cells and CCAAT/enhancer-binding proteins. GSK3β also is an important modulator of cell death, which may be a consequence of its regulatory effects on transcription factor activities. GSK3β facilitates apoptosis, and lithium's inhibition of GSK3β supports cell survival. Thus, signaling systems determining cell fate appear to be important targets of mood stabilizers, and these may include signaling pathways encompassing GSK3β, including transcription factors regulated by GSK3β.
KW - β-catenin
KW - Apoptosis
KW - Bipolar disorder
KW - CREB
KW - Lithium
KW - Neuroprotection
UR - http://www.scopus.com/inward/record.url?scp=0036214603&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0036214603&partnerID=8YFLogxK
U2 - 10.1038/sj/mp/4001017
DO - 10.1038/sj/mp/4001017
M3 - Article
C2 - 11986994
AN - SCOPUS:0036214603
VL - 7
JO - Molecular Psychiatry
JF - Molecular Psychiatry
SN - 1359-4184
IS - SUPPL. 1
ER -