Abstract
Glycogen Synthase Kinase 3 beta (GSK3β) is a serine-threonine kinase originally identified for its role in the conversion of glucose to glycogen. Pharmacological inhibition can be achieved by drug binding to ATP or magnesium binding sites on the enzyme. Pharmaceutical companies have developed several small molecule GSK3β inhibitors for diabetes research. Additionally, GSK3β inhibitors are being clinically tested as therapeutics for neurological diseases, however, the mechanisms of involvement are unclear. Several studies have shown that the therapeutic effect of GSK3β inhibition is associated with the inhibition of inflammation. Similarly, the mechanisms underlying the anti-inflammatory function of GSK3β inhibition are not well understood. GSK3β inhibition attenuates activation of the pro-inflammatory transcription factor NFκB, and activates the immuno-modulatory transcription factor β-catenin. GSK3β inhibition has also been shown to induce secretion of the anti-inflammatory cytokine IL-10. In addition, pharmacological inhibition of GSK3β suppressed alloreactive T-cell responses. The combined anti-proliferative and anti-inflammatory properties of small molecule inhibitors of GSK3β make them an attractive treatment modality towards the control of inflammation.
Keywords: GSK3β, Glycogen synthase kinase 3β, inflammation, T cells, immune system
Current Medicinal Chemistry
Title: Using Small Molecule GSK3β Inhibitors to Treat Inflammation
Volume: 17 Issue: 26
Author(s): G. Klamer, E. Song, K-H. Ko, T.A. O'Brien and A. Dolnikov
Affiliation:
Keywords: GSK3β, Glycogen synthase kinase 3β, inflammation, T cells, immune system
Abstract: Glycogen Synthase Kinase 3 beta (GSK3β) is a serine-threonine kinase originally identified for its role in the conversion of glucose to glycogen. Pharmacological inhibition can be achieved by drug binding to ATP or magnesium binding sites on the enzyme. Pharmaceutical companies have developed several small molecule GSK3β inhibitors for diabetes research. Additionally, GSK3β inhibitors are being clinically tested as therapeutics for neurological diseases, however, the mechanisms of involvement are unclear. Several studies have shown that the therapeutic effect of GSK3β inhibition is associated with the inhibition of inflammation. Similarly, the mechanisms underlying the anti-inflammatory function of GSK3β inhibition are not well understood. GSK3β inhibition attenuates activation of the pro-inflammatory transcription factor NFκB, and activates the immuno-modulatory transcription factor β-catenin. GSK3β inhibition has also been shown to induce secretion of the anti-inflammatory cytokine IL-10. In addition, pharmacological inhibition of GSK3β suppressed alloreactive T-cell responses. The combined anti-proliferative and anti-inflammatory properties of small molecule inhibitors of GSK3β make them an attractive treatment modality towards the control of inflammation.
Export Options
About this article
Cite this article as:
Klamer G., Song E., Ko K-H., O'Brien T.A. and Dolnikov A., Using Small Molecule GSK3β Inhibitors to Treat Inflammation, Current Medicinal Chemistry 2010; 17 (26) . https://dx.doi.org/10.2174/092986710792065090
DOI https://dx.doi.org/10.2174/092986710792065090 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...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
- Announcements
Related Articles
-
Viral Reservoirs an Impediment to HAART: New Strategies to Eliminate HIV-1
Current Drug Targets - Infectious Disorders Vasculogenic and Angiogenic Pathways in Moyamoya Disease
Current Medicinal Chemistry 5-HT3 Receptors
Current Drug Targets - CNS & Neurological Disorders Synthesis and Cytotoxic Evaluation of Quinazolin-4(3H)-one Derivatives Bearing Thiocarbamate, Thiourea or N-Methyldithiocarbamate Side Chains
Medicinal Chemistry Circulating Biomarkers for Tumor Angiogenesis: Where Are We?
Current Medicinal Chemistry Modification Strategies of Lipid-Based Nanocarriers for Mucosal Drug Delivery
Current Pharmaceutical Design Lycopene: A Review of Its Potential as an Anticancer Agent
Current Medicinal Chemistry - Anti-Cancer Agents Design, Synthesis and Biological Evaluation of a Phenyl Butyric Acid Derivative, N-(4-chlorophenyl)-4-phenylbutanamide: A HDAC6 Inhibitor with Anti-proliferative Activity on Cervix Cancer and Leukemia Cells
Anti-Cancer Agents in Medicinal Chemistry Syntheses and Preliminary Evaluation of Dual Target PET Probe [<sup>18</sup>F]-NOTA-Gly3- E (2PEG4-RGD-WH701) for PET Imaging of Breast Cancer
Anti-Cancer Agents in Medicinal Chemistry Mitochondria Damage in the Pathogenesis of Diabetic Retinopathy and in the Metabolic Memory Associated with its Continued Progression
Current Medicinal Chemistry Jatropha curcas: From Biodiesel Generation to Medicinal Applications
Recent Patents on Biotechnology Selective Cyclooxygenase-2 Inhibitors and Non-small Cell Lung Cancer
Current Medicinal Chemistry Anti-Cancer Compounds Targeted to VDAC: Potential and Perspectives
Current Medicinal Chemistry Aptamers: Potential Applications to Pancreatic Cancer Therapy
Anti-Cancer Agents in Medicinal Chemistry MicroRNAs: Potential Diagnostic and Therapeutic Targets for Breast Cancer
Epigenetic Diagnosis & Therapy (Discontinued) Characterization of the Lymphotropic Amplicons-6 and Tamplicon-7 Vectors Derived from HHV-6 and HHV-7
Current Gene Therapy From Natural Products to Small Molecule Ketone Histone Deacetylase Inhibitors: Development of New Class Specific Agents
Current Pharmaceutical Design Glycogen Synthase Kinase-3 Beta; A New Target in Pancreatic Cancer?
Current Cancer Drug Targets Pharmacology of Rhein and Advancement in the Synthesis of Its Derivatives
Current Traditional Medicine Site-related Effects of Relaxin in the Gastrointestinal Tract Through Nitric Oxide Signalling: An Updated Report
Current Protein & Peptide Science