Abstract
Since the discovery of phenothiazines as tau protein aggregation inhibitors, many additional small molecule inhibitors of diverse chemotype have been discovered and characterized in biological model systems. Although direct inhibition of tau aggregation has shown promise as a potential treatment strategy for depressing neurofibrillary lesion formation in Alzheimer’s disease, the mechanism of action of these compounds has been unclear. However, recent studies have found that tau aggregation antagonists exert their effects through both covalent and non-covalent means, and have identified associated potency and selectivity driving features. Here we review small-molecule tau aggregation inhibitors with a focus on compound structure and inhibitory mechanism. The elucidation of inhibitory mechanism has implications for maximizing on-target efficacy while minimizing off-target side effects.
Keywords: Alzheimer’s disease, aggregation, neurofibrillary tangle, paired helical filaments, tau.
Current Alzheimer Research
Title:Structure and Mechanism of Action of Tau Aggregation Inhibitors
Volume: 11 Issue: 10
Author(s): Katryna Cisek, Grace L. Cooper, Carol J. Huseby and Jeff Kuret
Affiliation:
Keywords: Alzheimer’s disease, aggregation, neurofibrillary tangle, paired helical filaments, tau.
Abstract: Since the discovery of phenothiazines as tau protein aggregation inhibitors, many additional small molecule inhibitors of diverse chemotype have been discovered and characterized in biological model systems. Although direct inhibition of tau aggregation has shown promise as a potential treatment strategy for depressing neurofibrillary lesion formation in Alzheimer’s disease, the mechanism of action of these compounds has been unclear. However, recent studies have found that tau aggregation antagonists exert their effects through both covalent and non-covalent means, and have identified associated potency and selectivity driving features. Here we review small-molecule tau aggregation inhibitors with a focus on compound structure and inhibitory mechanism. The elucidation of inhibitory mechanism has implications for maximizing on-target efficacy while minimizing off-target side effects.
Export Options
About this article
Cite this article as:
Cisek Katryna, Cooper L. Grace, Huseby J. Carol and Kuret Jeff, Structure and Mechanism of Action of Tau Aggregation Inhibitors, Current Alzheimer Research 2014; 11 (10) . https://dx.doi.org/10.2174/1567205011666141107150331
DOI https://dx.doi.org/10.2174/1567205011666141107150331 |
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
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
Diagnostic and therapeutic biomarkers of dementia
Dementia affects 18 million people worldwide. Dementia is a syndrome of symptoms caused by brain disease, usually chronic or progressive, clinically characterized by multiple impairments of higher cortical functions such as memory, thinking, orientation, and learning. In addition, in the course of dementia, cognitive deficits are observed, which often hinder ...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
-
Serum Biochemical Markers of Brain Injury
Mini-Reviews in Medicinal Chemistry Molecule of the Month
Current Topics in Medicinal Chemistry Antiglucocorticoids, Neurogenesis and Depression
Mini-Reviews in Medicinal Chemistry MicroRNA Regulatory Network in Human Colorectal Cancer
Mini-Reviews in Medicinal Chemistry Therapy in Prion Diseases: From Molecular and Cellular Biology to Therapeutic Targets
Infectious Disorders - Drug Targets Synthesis, Crystal Structure, Characterization and DNA Binding Studies of Novel Copper (II) Complex Based on Amino Acid Schiff Base
Current Organic Chemistry Therapeutic Application of Histone Deacetylase Inhibitors for Stroke
Central Nervous System Agents in Medicinal Chemistry Glioblastoma Tumor Initiating Cells: Therapeutic Strategies Targeting Apoptosis and MicroRNA Pathways
Current Molecular Medicine ABC Transporters in the Development of Multidrug Resistance in Cancer Therapy
Current Pharmaceutical Design Hybrid-Based Multi-Target Ligands for the Treatment of Alzheimer's Disease
Current Topics in Medicinal Chemistry Application of Proteomics to the Discovery of Cancer Biomarkers
Current Cancer Therapy Reviews Epigenetics in Alzheimers Disease: a Focus on DNA Modifications
Current Pharmaceutical Design Functional Multipotency of Stem Cells: A Conceptual Review of Neurotrophic Factor-Based Evidence and Its Role in Translational Research
Current Neuropharmacology Anionic Host Defence Peptides from the Plant Kingdom: Their Anticancer Activity and Mechanisms of Action
Protein & Peptide Letters Emerging β-Amyloid Therapies for the Treatment of Alzheimers Disease
Current Pharmaceutical Design Melatonin-mitochondria Interplay in Health and Disease
Current Topics in Medicinal Chemistry CD44 and EpCAM: Cancer-Initiating Cell Markers
Current Molecular Medicine Dehydroepiandrosterone and Its Derivatives: Potentially Novel Anti-Proliferative and Chemopreventive Agents
Current Pharmaceutical Design Peroxisome Proliferator Activated Receptor Gamma Coactivator 1 Alpha: An Emerging Target for Neuroprotection in Parkinson’s Disease
CNS & Neurological Disorders - Drug Targets Current Management of Neonatal Liver Tumors
Current Pediatric Reviews