The Wnt Signaling Pathway in Bipolar Disorder
- 1 October 2002
- journal article
- research article
- Published by SAGE Publications in The Neuroscientist
- Vol. 8 (5) , 497-511
- https://doi.org/10.1177/107385802237176
Abstract
The Wnt signaling pathway is a highly conserved pathway critical for proper embryonic development. However, recent evidence suggests that this pathway and one of its key enzymes, glycogen synthase kinase 3β, may play important roles in regulating synaptic plasticity, cell survival, and circadian rhythms in the mature CNS—all of which have been implicated in the pathophysiology and treatment of bipolar disorder. Furthermore, two structurally highly dissimilar medications used to treat bipolar disorder, lithium and valproic acid, exert effects on components of the Wnt signaling pathway. Together, these data suggest that the Wnt signaling pathway may play an important role in the treatment of bipolar disorder. Here, the authors review the modulation of the Wnt/GSK-3β signaling pathway by mood-stabilizing agents, focusing on two therapeutically relevant aspects: neuroprotection and modulation of circadian rhythms. The future development of selective GSK-3β inhibitors may have considerable utility not only for the treatment of bipolar disorder but also for a variety of classical neurodegenerative disorders.Keywords
This publication has 124 references indexed in Scilit:
- Somatic mutations ofWNT/wingless signaling pathway components in primitive neuroectodermal tumorsInternational Journal of Cancer, 2001
- Activation of glycogen synthase kinase 3 beta (GSK‐3β) by platelet activating factor mediates migration and cell death in cerebellar granule neuronsEuropean Journal of Neuroscience, 2001
- Glycogen synthase kinase-3β immunoreactivity is reduced in the prefrontal cortex in schizophreniaNeuroscience Letters, 2001
- Insulin and IGF-1 stimulate the β-catenin pathway through two signalling cascades involving GSK-3β inhibition and Ras activationOncogene, 2001
- Lithium Inhibits Glycogen Synthase Kinase-3 by Competition for MagnesiumBiochemical and Biophysical Research Communications, 2001
- A GSK3‐binding peptide from FRAT1 selectively inhibits the GSK3‐catalysed phosphorylation of Axin and β‐cateninFEBS Letters, 1999
- Glycogen synthase kinase-3β, β-catenin, and tau in postmortem bipolar brainJournal Of Neural Transmission-Parkinsons Disease and Dementia Section, 1999
- Lithium inhibits glycogen synthase kinase-3 activity and mimics Wingless signalling in intact cellsCurrent Biology, 1996
- Dysfunction of protein kinase FA/GSK‐3α in lymphocytes of patients with schizophrenic disorderJournal of Cellular Biochemistry, 1995
- The entire mesodermal mantle behaves as Spemann's organizer in dorsoanterior enhanced Xenopus laevis embryosDevelopmental Biology, 1988