Abstract
Alzheimer disease (AD) is the most common cause of dementia in adults. The current therapy for AD has only moderate efficacy in controlling symptoms, and it does not cure the disease. Recent studies have suggested that abnormal hyperphosphorylation of tau in the brain plays a vital role in the molecular pathogenesis of AD and in neurodegeneration. This article reviews the current advances in understanding of tau protein, regulation of tau phosphorylation, and the role of its abnormal hyperphosphorylation in neurofibrillary degeneration. Furthermore, several therapeutic strategies for treating AD on the basis of the important role of tau hyperphosphorylation in the pathogenesis of the disease are described. These strategies include (1) inhibition of glycogen synthase kinase-3β (GSK-3β), cyclin-dependent kinase 5 (cdk5), and other tau kinases; (2) restoration of PP2A activity; and (3) targeting tau O-GlcNAcylation. Development of drugs on the basis of these strategies is likely to lead to disease-modifying therapies for AD.
Keywords: Alzheimer disease, tau, neurodegeneration, GSK-3β, cdk5, protein phosphatases, O-GlcNAcylation, therapy
Current Medicinal Chemistry
Title: Hyperphosphorylation of Microtubule-Associated Protein Tau: A Promising Therapeutic Target for Alzheimer Disease
Volume: 15 Issue: 23
Author(s): C.-X. Gong and K. Iqbal
Affiliation:
Keywords: Alzheimer disease, tau, neurodegeneration, GSK-3β, cdk5, protein phosphatases, O-GlcNAcylation, therapy
Abstract: Alzheimer disease (AD) is the most common cause of dementia in adults. The current therapy for AD has only moderate efficacy in controlling symptoms, and it does not cure the disease. Recent studies have suggested that abnormal hyperphosphorylation of tau in the brain plays a vital role in the molecular pathogenesis of AD and in neurodegeneration. This article reviews the current advances in understanding of tau protein, regulation of tau phosphorylation, and the role of its abnormal hyperphosphorylation in neurofibrillary degeneration. Furthermore, several therapeutic strategies for treating AD on the basis of the important role of tau hyperphosphorylation in the pathogenesis of the disease are described. These strategies include (1) inhibition of glycogen synthase kinase-3β (GSK-3β), cyclin-dependent kinase 5 (cdk5), and other tau kinases; (2) restoration of PP2A activity; and (3) targeting tau O-GlcNAcylation. Development of drugs on the basis of these strategies is likely to lead to disease-modifying therapies for AD.
Export Options
About this article
Cite this article as:
Gong C.-X. and Iqbal K., Hyperphosphorylation of Microtubule-Associated Protein Tau: A Promising Therapeutic Target for Alzheimer Disease, Current Medicinal Chemistry 2008; 15 (23) . https://dx.doi.org/10.2174/092986708785909111
DOI https://dx.doi.org/10.2174/092986708785909111 |
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
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
Current advances in inherited cardiomyopathy
Describe in detail all novel advances in multimodality imaging related to inherited cardiomyopathy diagnosis and prognosis. Shed light to deeper phenotypic characterization. Acknowledge recent advances in genetics, genomics and precision medicineread 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
-
Antidepressant Related Movement Disorders in the Elderly
Current Psychiatry Reviews Atomoxetine Protects Against NMDA Receptor-mediated Hippocampal Neuronal Death Following Transient Global Cerebral Ischemia
Current Neurovascular Research From Multiple PAR1 Receptor/Protein Interactions to their Multiple Therapeutic Implications
Current Topics in Medicinal Chemistry Selective Serotonin-norepinephrine Re-uptake Inhibition Limits Renovas-cular-hypertension Induced Cognitive Impairment, Endothelial Dysfunction, and Oxidative Stress Injury
Current Neurovascular Research Administration of Exogenous Surfactant and Cytosolic Phospholipase A2α Inhibitors may Help COVID-19 Infected Patients with Chronic Diseases
Coronaviruses Neuroinflammation in Alzheimer’s Disease: Microglia, Molecular Participants and Therapeutic Choices
Current Alzheimer Research Applications of Integrated Data Mining Methods to Exploring Natural Product Space for Acetylcholinesterase Inhibitors
Combinatorial Chemistry & High Throughput Screening Aluminofluoride Complexes: Phosphate Analogues and a Hidden Hazard for Living Organisms
Current Inorganic Chemistry (Discontinued) SLC1 Glutamate Transporters and Diseases: Psychiatric Diseases and Pathological Pain
Current Molecular Pharmacology Relevance of the Chronobiological and Non-chronobiological Actions of Melatonin for Enhancing Therapeutic Efficacy in Neurodegenerative Disorders
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery Identification of Bioactive Natural Products by Pharmacophore-Based Virtual Screening
Current Pharmaceutical Design The Role of Microglia in Antibody-Mediated Clearance of Amyloid-Beta from the Brain
CNS & Neurological Disorders - Drug Targets Interacting with γSecretase for Treating Alzheimer's Disease: From Inhibition to Modulation
Current Medicinal Chemistry Nanotechnology for Alzheimer Disease
Current Alzheimer Research Molecular Linkages Between Diabetes and Alzheimer's Disease: Current Scenario and Future Prospects
CNS & Neurological Disorders - Drug Targets State-of-the-Art Methodologies for the Discovery and Characterization of DNA G-Quadruplex Binders
Current Pharmaceutical Design Vitamin D and Cardiovascular Disease: A Novel Agent for Reducing Cardiovascular Risk?
Current Vascular Pharmacology New Insights into the Roles of Endolysosomal Cathepsins in the Pathogenesis of Alzheimers Disease: Cathepsin Inhibitors as Potential Therapeutics
CNS & Neurological Disorders - Drug Targets Management of Hypertension in Relation to Acute Coronary Syndromes and Revascularisation
Current Pharmaceutical Design Signal Transduction by the Cytoplasmic Domain of NEUREGULIN-1 and its Roles During Neuronal Aging
Current Signal Transduction Therapy