Abstract
An intracellular hallmark of Alzheimer’s Disease (AD) is accumulation of hyperphosphorylated tau as paired helical filaments (PHF). A significant advance in understanding the behavior of tau occurred when it was reported that VQIVYK hexapeptide motif is responsible for initiating the process of aggregation. In the last years, a great number of Tau aggregation inhibitors have been developed, including flavonoids. However, the binding mode of these potential drugs is not well established. In this work, the behavior and conformational stability of the Tau hexapeptide306VQIVYK311 were investigated in the presence of two known flavonoid inhibitors using Molecular Interaction Fields (MIFs), pharmacophore perception and molecular dynamics (MD) simulations. We have also proposed a likely binding mode for such inhibitors with the hexapeptide, which agrees with experimental data and is able to explain structure-activity relationships between different flavonoids.
Keywords: Alzheimer’s disease, tau protein, flavonoids, molecular interaction fields, pharmacophore perception, molecular dynamics simulations
Current Bioactive Compounds
Title:In Silico Binding Mode Proposed for Flavonoid Ligands of Tau Protein with Interest in Alzheimer's Disease
Volume: 9 Issue: 1
Author(s): Susimaire Pedersoli-Mantoani, Carlos Henrique Tomich de Paula da Silva and Vinicius Barreto da Silva
Affiliation:
Keywords: Alzheimer’s disease, tau protein, flavonoids, molecular interaction fields, pharmacophore perception, molecular dynamics simulations
Abstract: An intracellular hallmark of Alzheimer’s Disease (AD) is accumulation of hyperphosphorylated tau as paired helical filaments (PHF). A significant advance in understanding the behavior of tau occurred when it was reported that VQIVYK hexapeptide motif is responsible for initiating the process of aggregation. In the last years, a great number of Tau aggregation inhibitors have been developed, including flavonoids. However, the binding mode of these potential drugs is not well established. In this work, the behavior and conformational stability of the Tau hexapeptide306VQIVYK311 were investigated in the presence of two known flavonoid inhibitors using Molecular Interaction Fields (MIFs), pharmacophore perception and molecular dynamics (MD) simulations. We have also proposed a likely binding mode for such inhibitors with the hexapeptide, which agrees with experimental data and is able to explain structure-activity relationships between different flavonoids.
Export Options
About this article
Cite this article as:
Pedersoli-Mantoani Susimaire, Henrique Tomich de Paula da Silva Carlos and Barreto da Silva Vinicius, In Silico Binding Mode Proposed for Flavonoid Ligands of Tau Protein with Interest in Alzheimer's Disease, Current Bioactive Compounds 2013; 9 (1) . https://dx.doi.org/10.2174/1573407211309010004
DOI https://dx.doi.org/10.2174/1573407211309010004 |
Print ISSN 1573-4072 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6646 |
- 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
-
Conference Report: Nanotechnology Congress & Expo 2015, Frankfurt, Germany August 11-13, 2015
CNS & Neurological Disorders - Drug Targets Current Pharmacological Approaches to Prevent and Treat Post- Menopausal Osteoporosis
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery (Discontinued) Hippocampal Mean Diffusivity for the Diagnosis of Dementia and Mild Cognitive Impairment in Primary Care
Current Alzheimer Research Effectiveness of Nasal Continuous Positive Airway Pressure (CPAP) Therapy on Cardiovascular Outcomes in Obstructive Sleep Apnea-Hypopnea Syndrome (OSAHS)
Current Respiratory Medicine Reviews 25OH-Vitamin D3 Levels in Obesity and Metabolic Syndrome—Unaltered in Young and not Correlated to Carotid IMT in All Ages
Current Pharmaceutical Design New Targets for Treating the Underlying Pathophysiology and Nonmotor Aspects of Parkinson's Disease
CNS & Neurological Disorders - Drug Targets PET Tracers for Serotonin Receptors and Their Applications
Central Nervous System Agents in Medicinal Chemistry Large-Scale Prediction of Drug Targets Based on Local and Global Consistency of Chemical-Chemical Networks
Combinatorial Chemistry & High Throughput Screening Effects of Diabetic HDL on Endothelial Cell Function
Cardiovascular & Hematological Disorders-Drug Targets A Nanotechnological Approach to the Management of Alzheimer Disease and Type 2 Diabetes
CNS & Neurological Disorders - Drug Targets Synthesis and Biological Evaluation of Berberine Derivatives as IBS Modulator
Letters in Drug Design & Discovery Patent Selections:
Recent Patents on Regenerative Medicine Potential New Targets for Antithrombotic Therapy
Current Pharmaceutical Design Therapeutic Approach for Neuronal Disease by Regulating Reninangiotensin System
Current Hypertension Reviews Hyponatraemia Associated with Trimethoprim Use
Current Drug Safety Serotonin 5-HT6 Receptor Antagonists for the Treatment of Alzheimers Disease
Current Topics in Medicinal Chemistry Diabetes and Complications: Cellular Signaling Pathways, Current Understanding and Targeted Therapies
Current Drug Targets Microglial dependent protective effects of neuroactive steroids
CNS & Neurological Disorders - Drug Targets Natural Compounds A Weapon to Ameliorate Breast Cancer Cells: A Review
Anti-Cancer Agents in Medicinal Chemistry Atorvastatin May Correct Dyslipidemia in Adult Patients at Risk for Alzheimer’s Disease Through an Anti-Inflammatory Pathway
CNS & Neurological Disorders - Drug Targets