Abstract
Abnormal interactions of Zn2+ and Cu2+ with the amyloid β-peptide (Aβ) are proposed to play an important role in the neuropathogenesis of Alzheimer’s disease (AD). Metal chelators are potential therapeutic agents for AD because they could sequester metals ions from Aβ aggregates and reverse the aggregation. In this study, two nitrogencontaining ligands, TACN and BPA, have been investigated as possible metal chelators in the therapy of Alzheimer’s disease. The interactions between the chelators and Aβ40 aggregates are studied by turbidometry, thioflavin T (ThT) fluorescence spectroscopy, inductively coupled plasma mass spectrometry (ICP-MS), BCA protein assay, circular dichroism spectroscopy (CD), and atomic force microscopy (AFM). The results demonstrates that TACN and BPA are capable of both disrupting and preventing Zn2+ or Cu2+-induced Aβ40 aggregation. Moreover, they can also suppress the production of H2O2 induced by Cu-Aβ40, associated with toxic oxidative stress in AD.
Keywords: Alzheimer’s disease, Amyloid β-peptide, Metal, Chelators.
CNS & Neurological Disorders - Drug Targets
Title:Two Nitrogen-containing Ligands as Inhibitors of Metal-Induced Amyloid β-Peptide Aggregation
Volume: 13 Issue: 1
Author(s): Tingting Chen, Shajun Zhu, Siyuan Liu, Yapeng Lu and Li Zhu
Affiliation:
Keywords: Alzheimer’s disease, Amyloid β-peptide, Metal, Chelators.
Abstract: Abnormal interactions of Zn2+ and Cu2+ with the amyloid β-peptide (Aβ) are proposed to play an important role in the neuropathogenesis of Alzheimer’s disease (AD). Metal chelators are potential therapeutic agents for AD because they could sequester metals ions from Aβ aggregates and reverse the aggregation. In this study, two nitrogencontaining ligands, TACN and BPA, have been investigated as possible metal chelators in the therapy of Alzheimer’s disease. The interactions between the chelators and Aβ40 aggregates are studied by turbidometry, thioflavin T (ThT) fluorescence spectroscopy, inductively coupled plasma mass spectrometry (ICP-MS), BCA protein assay, circular dichroism spectroscopy (CD), and atomic force microscopy (AFM). The results demonstrates that TACN and BPA are capable of both disrupting and preventing Zn2+ or Cu2+-induced Aβ40 aggregation. Moreover, they can also suppress the production of H2O2 induced by Cu-Aβ40, associated with toxic oxidative stress in AD.
Export Options
About this article
Cite this article as:
Chen Tingting, Zhu Shajun, Liu Siyuan, Lu Yapeng and Zhu Li, Two Nitrogen-containing Ligands as Inhibitors of Metal-Induced Amyloid β-Peptide Aggregation, CNS & Neurological Disorders - Drug Targets 2014; 13 (1) . https://dx.doi.org/10.2174/18715273113129990076
DOI https://dx.doi.org/10.2174/18715273113129990076 |
Print ISSN 1871-5273 |
Publisher Name Bentham Science Publisher |
Online ISSN 1996-3181 |
Call for Papers in Thematic Issues
Diagnosis and treatment of central nervous system infectious diseases
Infectious diseases of the central nervous system (CNS) can be divided into bacterial, tuberculous, viral, fungal, parasitic infections, etc. Early etiological treatment is often the most crucial means to reduce the mortality rate of patients with central nervous system infections, reduce complications and sequelae, and improve prognosis. The initial clinical ...read more
Techniques of Drug Repurposing: Delivering a new life to Herbs & Drugs
Of late, with the adaptation of innovative approaches and integration of advancements made towards medical sciences as well as the availability of a wide range of tools; several therapeutic challenges are being translated into viable clinical solutions, with a high degree of efficacy, safety, and selectivity. With a better understanding ...read more
Trends and perspectives in the rational management of CNS disorders
Central nervous system (CNS) diseases enforce a significant global health burden, driving ongoing efforts to improve our understanding and effectiveness of therapy. This issue investigates current advances in the discipline, focusing on the understanding as well as therapeutic handling of various CNS diseases. The issue covers a variety of diseases, ...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
Related Articles
-
Patterns of Cognitive Impairment in Neurological Disease
Current Psychiatry Reviews Protein Homeostasis as a Therapeutic Target for Diseases of Protein Conformation
Current Topics in Medicinal Chemistry Advances in Drug Delivery from Nose to Brain: An Overview
Current Drug Therapy Neural Stem Cells: From Neurobiology to Clinical Applications
Current Pharmaceutical Biotechnology Autophagy Enhancer Carbamazepine Alleviates Memory Deficits and Cerebral Amyloid-β Pathology in a Mouse Model of Alzheimer's Disease
Current Alzheimer Research Cholesterol, Alzheimers Disease, Prion Disorders: A menage a trois?
Current Drug Targets Mesenchymal Stem Cells of Dental Origin-Their Potential for Antiinflammatory and Regenerative Actions in Brain and Gut Damage
Current Neuropharmacology Clinical and Rehabilitative Management of Retinitis Pigmentosa:Up-to-Date
Current Genomics Stem Cells: An Overview of the Current Status of Therapies for Central and Peripheral Nervous System Diseases
Current Medicinal Chemistry Silencing of Disease-related Genes by Small Interfering RNAs
Current Molecular Medicine Basic Pharmacology of NMDA Receptors
Current Pharmaceutical Design The Neurovascular Unit: Focus on the Regulation of Arterial Smooth Muscle Cells
Current Neurovascular Research Neurodegeneration in the Pathogenesis of Diabetic Retinopathy: Molecular Mechanisms and Therapeutic Implications
Current Medicinal Chemistry Editorial [Hot Topic: Auditory Processing Disorder (Guest Editors: Vasiliki Maria Iliadou)]
Current Pediatric Reviews The Molecular and Pharmacological Mechanisms of HIV-Related Neuropathic Pain
Current Neuropharmacology Chemistry and Biology of Thyrotropin-Releasing Hormone (TRH) and its Analogs
Current Medicinal Chemistry Cardiac ATP-Sensitive Potassium Channels: A Potential Target for an Anti-Ischaemic Pharmacological Strategy
Cardiovascular & Hematological Agents in Medicinal Chemistry Deciphering the Role of Aberrant Protein Post-Translational Modification in the Pathology of Neurodegeneration
CNS & Neurological Disorders - Drug Targets Chemical Composition, Antioxidant, Alpha-glucosidase Inhibitory, Anticholinesterase and Photoprotective Activities of the Aerial Parts of <i>Schinus molle</i> L.
Current Bioactive Compounds Neuroprotective Effects of Ellagitannins: A Brief Review
Current Drug Targets