Abstract
Alzheimers disease (AD) is a common neurodegenerative disorder that presents clinically as inexorable cognitive impairment and decline in performance of activities of daily living. AD is characterized pathologically by neuronal depopulation, extracellular amyloid plaques, and intraneuronal accumulation of neurofibrillary tangles (NFTs). Accumulation of these polypeptide aggregates is generally believed to be integral to the pathogenesis of AD. Recent evidence implicates the protein kinase glycogen synthase kinase 3 (GSK-3) in the regulation of both of these processes. GSK-3 has long been studied as one of several tau protein kinases, and has more recently been shown to be involved in the generation of Aβ peptides. GSK-3 activity may also promote cell death and conversely, inhibition of GSK-3 has been associated with increased cell survival under a variety of cytotoxic conditions. Thus drugs that target GSK-3 could attack AD pathogenesis on multiple fronts simultaneously. Here we will briefly review the molecular understanding of AD pathogenesis as it stands at this point, and then discuss the emerging role of GSK-3 in regulating these processes.
Keywords: Lithium, Paullones, GSK-3 binding protein (GBP), Indirubins, Carcinogenesis
Current Drug Targets
Title: Multiple Roles for Glycogen Synthase Kinase-3 as a Drug Target in Alzheimers Disease
Volume: 7 Issue: 11
Author(s): Hui-Chuan Huang and Peter S. Klein
Affiliation:
Keywords: Lithium, Paullones, GSK-3 binding protein (GBP), Indirubins, Carcinogenesis
Abstract: Alzheimers disease (AD) is a common neurodegenerative disorder that presents clinically as inexorable cognitive impairment and decline in performance of activities of daily living. AD is characterized pathologically by neuronal depopulation, extracellular amyloid plaques, and intraneuronal accumulation of neurofibrillary tangles (NFTs). Accumulation of these polypeptide aggregates is generally believed to be integral to the pathogenesis of AD. Recent evidence implicates the protein kinase glycogen synthase kinase 3 (GSK-3) in the regulation of both of these processes. GSK-3 has long been studied as one of several tau protein kinases, and has more recently been shown to be involved in the generation of Aβ peptides. GSK-3 activity may also promote cell death and conversely, inhibition of GSK-3 has been associated with increased cell survival under a variety of cytotoxic conditions. Thus drugs that target GSK-3 could attack AD pathogenesis on multiple fronts simultaneously. Here we will briefly review the molecular understanding of AD pathogenesis as it stands at this point, and then discuss the emerging role of GSK-3 in regulating these processes.
Export Options
About this article
Cite this article as:
Huang Hui-Chuan and Klein S. Peter, Multiple Roles for Glycogen Synthase Kinase-3 as a Drug Target in Alzheimers Disease, Current Drug Targets 2006; 7 (11) . https://dx.doi.org/10.2174/1389450110607011389
DOI https://dx.doi.org/10.2174/1389450110607011389 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
- 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
-
ADAM Proteases: Protective Role in Alzheimers and Prion Diseases ?
Current Alzheimer Research Multi-Target Inhibitors for Proteins Associated with Alzheimer: In Silico Discovery using Fragment-Based Descriptors
Current Alzheimer Research Design, Synthesis and Evaluation of 2,4,6-substituted Pyrimidine Derivatives as BACE-1 Inhibitor: Plausible Lead for Alzheimer’s Disease
Medicinal Chemistry Meta-Analysis of Creatine for Neuroprotection Against Parkinson’s Disease
CNS & Neurological Disorders - Drug Targets Position Based Nucleotide Analysis of miR168 Family in Higher Plants and its Targets in Mammalian Transcripts
MicroRNA Genotoxicity in Alzheimers Disease: Role of Amyloid
Current Alzheimer Research Insulin and the Future Treatment of Alzheimer’s Disease
CNS & Neurological Disorders - Drug Targets C. elegans as Model for Drug Discovery
Current Topics in Medicinal Chemistry Fullerenes: From Carbon to Nanomedicine
Mini-Reviews in Medicinal Chemistry Evaluation of Venom as a Promising Tool for Drug Discovery: Focusing on Neurological Disorders
Venoms and Toxins Current Treatment Options for Alzheimer’s Disease and Parkinson’s Disease Dementia
Current Neuropharmacology Aging in Down Syndrome and the Development of Alzheimer’s Disease Neuropathology
Current Alzheimer Research Thiazoles and Thiazolidinones as Antioxidants
Current Medicinal Chemistry Frontotemporal Lobar Degeneration (FTLD): Review and Update for Clinical Neurologists
Current Alzheimer Research Inflammation as Therapeutic Objective in Stroke
Current Pharmaceutical Design Patent Annotations
Recent Patents on Cardiovascular Drug Discovery The Stress Rheostat: An Interplay Between the Unfolded Protein Response (UPR) and Autophagy in Neurodegeneration
Current Molecular Medicine Small Molecule Modulation of p75 Neurotrophin Receptor Functions
CNS & Neurological Disorders - Drug Targets Current Development in Encapsulated Cell Therapy for Degenerative Retinopathies
Current Tissue Engineering (Discontinued) Relationship between chronic disturbance of 2,3-diphosphoglycerate metabolism in erythrocytes and Alzheimer disease
CNS & Neurological Disorders - Drug Targets