Abstract
Tau aggregation is an appealing target for therapeutic intervention. However, conformational change or aggregation needs to be targeted without inhibiting the normal biology of tau and its role in microtubule stabilization. The number of compound classes being tested at this time are very limited and include Congo red derivatives [1], anthraquinones (Pickhardt et al. 2005 [2], disputed in Crowe et al. 2007 [3]), 2,3-di(furan-2-yl)-quinoxalines , phenylthiazolyl-hydrazide (PTH) [4], polyphenols and porphyrins [5] and cyanine dyes [6-8]. Herein we have utilized a member of the cyanine dye family (C11) in an organotypic slice culture model of tangle formation. Our results demonstrate that C11 is capable of affecting tau polymerization in a biphasic, dose dependent manner. At submicromolar concentrations (0.001 μM) C11 reduced levels of aggregated tau. However, higher doses resulted in an increase in tau polymerization. These effects can also be seen at the level of individual filaments with changes in filament length and number mirroring the pattern seen via immunoblotting. In addition, this effect is achieved without altering levels of phosphorylation at disease and microtubule binding relevant epitopes.
Keywords: Alzheimer disease, tau, tangle, cyanine, phosphorylation, polymerization
Current Alzheimer Research
Title: Disaggregation of Tau as a Therapeutic Approach to Tauopathies
Volume: 7 Issue: 3
Author(s): K. Duff, J. Kuret and E.E Congdon
Affiliation:
Keywords: Alzheimer disease, tau, tangle, cyanine, phosphorylation, polymerization
Abstract: Tau aggregation is an appealing target for therapeutic intervention. However, conformational change or aggregation needs to be targeted without inhibiting the normal biology of tau and its role in microtubule stabilization. The number of compound classes being tested at this time are very limited and include Congo red derivatives [1], anthraquinones (Pickhardt et al. 2005 [2], disputed in Crowe et al. 2007 [3]), 2,3-di(furan-2-yl)-quinoxalines , phenylthiazolyl-hydrazide (PTH) [4], polyphenols and porphyrins [5] and cyanine dyes [6-8]. Herein we have utilized a member of the cyanine dye family (C11) in an organotypic slice culture model of tangle formation. Our results demonstrate that C11 is capable of affecting tau polymerization in a biphasic, dose dependent manner. At submicromolar concentrations (0.001 μM) C11 reduced levels of aggregated tau. However, higher doses resulted in an increase in tau polymerization. These effects can also be seen at the level of individual filaments with changes in filament length and number mirroring the pattern seen via immunoblotting. In addition, this effect is achieved without altering levels of phosphorylation at disease and microtubule binding relevant epitopes.
Export Options
About this article
Cite this article as:
Duff K., Kuret J. and Congdon E.E, Disaggregation of Tau as a Therapeutic Approach to Tauopathies, Current Alzheimer Research 2010; 7 (3) . https://dx.doi.org/10.2174/156720510791050885
DOI https://dx.doi.org/10.2174/156720510791050885 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
Call for Papers in Thematic Issues
New Advances in the Prevention, Diagnosis, Treatment, and Rehabilitation of Alzheimer's Disease
Aims and Scope: Introduction: Alzheimer's disease (AD) poses a significant global health challenge, with an increasing prevalence that demands concerted efforts to advance our understanding and strategies for prevention, diagnosis, treatment, and rehabilitation. This thematic issue aims to bring together cutting-edge research and innovative approaches from multidisciplinary perspectives to address ...read more
Alzheimer's Disease Drug Development
Alzheimer's disease is a progressive neurodegenerative disorder that affects millions of people worldwide. Despite decades of research, no cure or disease-modifying treatment is available yet. Therefore, the need for developing effective therapies to treat Alzheimer's disease is an urgent matter. This special issue aims to provide a comprehensive overview of ...read more
Current updates on the Role of Neuroinflammation in Neurodegenerative Disorders
Neuroinflammation is an invariable hallmark of chronic and acute neurodegenerative disorders and has long been considered a potential drug target for Alzheimer?s disease (AD) and dementia. Significant evidence of inflammatory processes as a feature of AD is provided by the presence of inflammatory markers in plasma, CSF and postmortem brain ...read more
Deep Learning for Advancing Alzheimer's Disease Research
Alzheimer's disease (AD) poses a significant global health challenge, with an increasing number of individuals affected yearly. Deep learning, a subfield of artificial intelligence, has shown immense potential in various domains, including healthcare. This thematic issue of Current Alzheimer Research explores the application of deep learning techniques in advancing our ...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
-
Oxidative Stress and Neurodegenerative Diseases: A Review of Upstream and Downstream Antioxidant Therapeutic Options
Current Neuropharmacology Non-Analgesic Effects of Opioids: Neuroprotection in the Retina
Current Pharmaceutical Design Patent Selections
Recent Patents on CNS Drug Discovery (Discontinued) The NF-kB Pathway as a Potential Target for Autoimmune Disease Therapy
Current Pharmaceutical Design Increased Paternal Age and Child Health and Development
Current Pediatric Reviews Homology Modeling of Human Kynurenine Aminotransferase III and Observations on Inhibitor Binding Using Molecular Docking
Central Nervous System Agents in Medicinal Chemistry Role of Inflammatory Markers in Elderly Type 2 Diabetic Patients with Mild Cognitive Impairment
Current Diabetes Reviews Message from the Editor-in-Chief
CNS & Neurological Disorders - Drug Targets Current Status and Challenges in Rotigotine Delivery
Current Pharmaceutical Design The Protective Effect of Jatrorrhizine Against Oxidative Stress in Primary Rat Cortical Neurons
CNS & Neurological Disorders - Drug Targets Reducing Rifle Bolt Carrier Bounce
Recent Patents on Mechanical Engineering Clinical Management of the Cardiovascular Failure in Sepsis
Current Vascular Pharmacology Immunosuppressive Therapies in Solid Organ Transplantation
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) Gastrodia Elata Bl Attenuates Methamphetamine-Induced Dopaminergic Toxicity Via Inhibiting Oxidative Burdens
Current Neuropharmacology Validation of the Neuroinflammation Cycle as a Drug Discovery Target Using Integrative Chemical Biology and Lead Compound Development with an Alzheimers Disease-Related Mouse Model
Current Alzheimer Research Application of Microdialysis in Clinical Pharmacology
Current Clinical Pharmacology Early Intervention in Psychosis: Rationale, Results and Implications for Treatment of Adolescents at Risk
Adolescent Psychiatry The Molecular Basis of Memantine Action in Alzheimers Disease and Other Neurologic Disorders: Low-affinity, Uncompetitive Antagonism
Current Alzheimer Research Maternal Nutrient Restriction is not Equivalent to Maternal Biological Stress
Current Drug Targets Role of Catechol-O-Methyltransferase (COMT)-Dependent Processes in Parkinson’s Disease and L-DOPA Treatment
CNS & Neurological Disorders - Drug Targets