Abstract
There exists an immediate need to develop novel medications for the treatment of mood disorders such as bipolar disorder and depression. Initial interest in glycogen synthase kinase-3 (GSK-3) as a target for the treatment of mood disorders arose from the finding that the mood stabilizing drug lithium directly inhibited the enzyme. More recent preclinical evidence implicates the modulation of GSK- 3 in either the direct or downstream mechanism of action of many other mood stabilizer and antidepressant medications currently in use. One of the cellular targets of GSK-3, which may mediate some of the effects of lithium and other drugs, is β-catenin, a transcription factor that is rapidly degraded when GSK-3 is active. Recent rodent behavioral data (both genetic and pharmacological) supports GSK-3 representing a therapeutically relevant target of lithium. This includes antidepressant-like behavior in the forced swim test and antimaniclike response to amphetamine following administration of the GSK-3 inhibitor AR-A014418, a findings that is concomitant with an increase in brain β-catenin. The evidence described in this review suggests that regulating GSK-3 may represent a target for novel medications to treat mood disorders.
Keywords: Manic-depressive illness, psychopharmacology, mania, depression, mood stabilizer, antidepressant, valproate
Current Drug Targets
Title: Targeting Glycogen Synthase Kinase-3 in the CNS: Implications for the Development of New Treatments for Mood Disorders
Volume: 7 Issue: 11
Author(s): Todd D. Gould, Alyssa M. Picchini, Haim Einat and Husseini K. Manji
Affiliation:
Keywords: Manic-depressive illness, psychopharmacology, mania, depression, mood stabilizer, antidepressant, valproate
Abstract: There exists an immediate need to develop novel medications for the treatment of mood disorders such as bipolar disorder and depression. Initial interest in glycogen synthase kinase-3 (GSK-3) as a target for the treatment of mood disorders arose from the finding that the mood stabilizing drug lithium directly inhibited the enzyme. More recent preclinical evidence implicates the modulation of GSK- 3 in either the direct or downstream mechanism of action of many other mood stabilizer and antidepressant medications currently in use. One of the cellular targets of GSK-3, which may mediate some of the effects of lithium and other drugs, is β-catenin, a transcription factor that is rapidly degraded when GSK-3 is active. Recent rodent behavioral data (both genetic and pharmacological) supports GSK-3 representing a therapeutically relevant target of lithium. This includes antidepressant-like behavior in the forced swim test and antimaniclike response to amphetamine following administration of the GSK-3 inhibitor AR-A014418, a findings that is concomitant with an increase in brain β-catenin. The evidence described in this review suggests that regulating GSK-3 may represent a target for novel medications to treat mood disorders.
Export Options
About this article
Cite this article as:
Gould D. Todd, Picchini M. Alyssa, Einat Haim and Manji K. Husseini, Targeting Glycogen Synthase Kinase-3 in the CNS: Implications for the Development of New Treatments for Mood Disorders, Current Drug Targets 2006; 7 (11) . https://dx.doi.org/10.2174/1389450110607011399
DOI https://dx.doi.org/10.2174/1389450110607011399 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
Call for Papers in Thematic Issues
New drug therapy for eye diseases
Eyesight is one of the most critical senses, accounting for over 80% of our perceptions. Our quality of life might be significantly affected by eye disease, including glaucoma, diabetic retinopathy, dry eye, etc. Although the development of microinvasive ocular surgery reduces surgical complications and improves overall outcomes, medication therapy is ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Vasoactive Intestinal Peptide in Neurodevelopmental Disorders:Therapeutic Potential
Current Pharmaceutical Design Properties of Neurotoxic Peptides Related to the Bri Gene
Protein & Peptide Letters Targeting Vesicle Trafficking: An Important Approach to Cancer Chemotherapy
Recent Patents on Anti-Cancer Drug Discovery New Perspectives in Glioma Immunotherapy
Current Pharmaceutical Design Sulfur Containing Acridine Derivatives in Preclinical Studies with Cancer Cell Lines
Current Medicinal Chemistry Quantitative Characterization of Phenotypical Markers After Differentiation of SH-SY5Y Cells
CNS & Neurological Disorders - Drug Targets Interactions of Iron Oxide Nanoparticles with the Immune System: Challenges and Opportunities for their Use in Nano-oncology
Current Pharmaceutical Design P2X7 Receptor Orchestrates Multiple Signalling Pathways Triggering Inflammation, Autophagy and Metabolic/Trophic Responses
Current Medicinal Chemistry Assessment of Signal Peptides to Optimize Interleukin 2 (IL-2) Folding and Expression
Current Proteomics Multifunctional Proteins in Tumorigenesis: Aminoacyl-tRNA Synthetases and Translational Components
Current Proteomics Emerging Proof of Protein Misfolding and Interactions in Multifactorial Alzheimer's Disease
Current Topics in Medicinal Chemistry Marginal Vitamin A Deficiency Exacerbates Memory Deficits Following Aβ1-42 Injection in Rats
Current Alzheimer Research Resisting the Resistance in Cancer: Cheminformatics Studies on Short- Path Base Excision Repair Pathway Antagonists Using Supervised Learning Approaches
Combinatorial Chemistry & High Throughput Screening Up-Regulation of Hypoxia-Inducible Factor (HIF)-1α and HIF-Target Genes in Cortical Neurons by the Novel Multifunctional Iron Chelator Anti-Alzheimer Drug, M30
Current Alzheimer Research The Role of ING Tumor Suppressors in UV Stress Response and Melanoma Progression
Current Drug Targets Granular Non-Fibrillar Aggregates and Toxicity in Alzheimer’s Disease
Current Alzheimer Research Therapeutic Perspectives of Inhibitors of Endocannabinoid Degradation
Current Drug Targets - CNS & Neurological Disorders DNA Microarray-Based Gene Expression Profiling in Cancer: Aiding Cancer Diagnosis, Assessing Prognosis and Predicting Response to Therapy
Current Pharmacogenomics Insights into a Critical Role of the FOXO3a-FOXM1 Axis in DNA Damage Response and Genotoxic Drug Resistance
Current Drug Targets Proteomic Analysis of Glioma Chemoresistance
Current Neuropharmacology