Abstract
The deposition of abnormal protein fibrils is a prominent pathological feature of many different ‘protein conformational’ diseases, including some important neurodegenerative diseases such as Alzheimers disease (AD), Parkinsons disease (PD), motor neurone disease and the ‘prion’ dementias. Some of the fibril-forming proteins or peptides associated with these diseases have been shown to be toxic to cells in culture. A clear understanding of the molecular mechanisms responsible for this toxicity should shed light on the probable link between protein deposition and cell loss in these diseases. In the case of the β-amyloid (Aβ), which accumulates in the brain in AD, there is good evidence that the toxic mechanism involves the production of reactive oxygen species (ROS). By means of an electron spin resonance (ESR) spin-trapping method, we have shown recently that solutions of Aβ liberate readily detectable amounts of hydroxyl radicals upon incubation in vitro followed by the addition of small amounts of Fe(II). We have also obtained similar results with α-synuclein, which accumulates in Lewy bodies in PD. Our data suggest that hydrogen peroxide accumulates during Aβ or α-synuclein incubation and that this is subsequently converted to hydroxyl radicals, on addition of Fe (II), by Fentons reaction. Consequently, we now support the idea that one of the fundamental molecular mechanisms underlying the pathogenesis of cell death in AD, PD, and possibly some other protein conformational diseases, could be the direct production of ROS during formation of the abnormal protein aggregates. This hypothesis suggests a novel approach to the therapy of this group of diseases.
Current Topics in Medicinal Chemistry
Title: Production of Reactive Oxygen Species from Aggregating Proteins Implicated in Alzheimers Disease, Parkinsons Disease and Other Neurodegenerative Diseases
Volume: 1 Issue: 6
Author(s): Brian J. Tabner, Stuart Turnbull, Omar M.A. El-Agnaf and David Allsop
Affiliation:
Abstract: The deposition of abnormal protein fibrils is a prominent pathological feature of many different ‘protein conformational’ diseases, including some important neurodegenerative diseases such as Alzheimers disease (AD), Parkinsons disease (PD), motor neurone disease and the ‘prion’ dementias. Some of the fibril-forming proteins or peptides associated with these diseases have been shown to be toxic to cells in culture. A clear understanding of the molecular mechanisms responsible for this toxicity should shed light on the probable link between protein deposition and cell loss in these diseases. In the case of the β-amyloid (Aβ), which accumulates in the brain in AD, there is good evidence that the toxic mechanism involves the production of reactive oxygen species (ROS). By means of an electron spin resonance (ESR) spin-trapping method, we have shown recently that solutions of Aβ liberate readily detectable amounts of hydroxyl radicals upon incubation in vitro followed by the addition of small amounts of Fe(II). We have also obtained similar results with α-synuclein, which accumulates in Lewy bodies in PD. Our data suggest that hydrogen peroxide accumulates during Aβ or α-synuclein incubation and that this is subsequently converted to hydroxyl radicals, on addition of Fe (II), by Fentons reaction. Consequently, we now support the idea that one of the fundamental molecular mechanisms underlying the pathogenesis of cell death in AD, PD, and possibly some other protein conformational diseases, could be the direct production of ROS during formation of the abnormal protein aggregates. This hypothesis suggests a novel approach to the therapy of this group of diseases.
Export Options
About this article
Cite this article as:
Brian J. Tabner , Stuart Turnbull , Omar M.A. El-Agnaf and David Allsop , Production of Reactive Oxygen Species from Aggregating Proteins Implicated in Alzheimers Disease, Parkinsons Disease and Other Neurodegenerative Diseases, Current Topics in Medicinal Chemistry 2001; 1 (6) . https://dx.doi.org/10.2174/1568026013394822
DOI https://dx.doi.org/10.2174/1568026013394822 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
Call for Papers in Thematic Issues
Chemistry Based on Natural Products for Therapeutic Purposes
The development of new pharmaceuticals for a wide range of medical conditions has long relied on the identification of promising natural products (NPs). There are over sixty percent of cancer, infectious illness, and CNS disease medications that include an NP pharmacophore, according to the Food and Drug Administration. Since NP ...read more
Current Trends in Drug Discovery Based on Artificial Intelligence and Computer-Aided Drug Design
Drug development discovery has faced several challenges over the years. In fact, the evolution of classical approaches to modern methods using computational methods, or Computer-Aided Drug Design (CADD), has shown promising and essential results in any drug discovery campaign. Among these methods, molecular docking is one of the most notable ...read more
Drug Discovery in the Age of Artificial Intelligence
In the age of artificial intelligence (AI), we have witnessed a significant boom in AI techniques for drug discovery. AI techniques are increasingly integrated and accelerating the drug discovery process. These developments have not only attracted the attention of academia and industry but also raised important questions regarding the selection ...read more
From Biodiversity to Chemical Diversity: Focus of Flavonoids
Flavonoids are the largest group of polyphenols, plant secondary metabolites arising from the essential aromatic amino acid phenylalanine (or more rarely from tyrosine) via the phenylpropanoid pathway. The flavan nucleus is the basic 15-carbon skeleton of flavonoids (C6-C3-C6), which consists of two phenyl rings (A and B) and a heterocyclic ...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
-
Early β-Amyloid-induced Synaptic Dysfunction Is Counteracted by Estrogen in Organotypic Hippocampal Cultures
Current Alzheimer Research Reduction of β-Amyloid Accumulation by Reticulon 3 in Transgenic Mice
Current Alzheimer Research Neuroprotection by Diazoxide in Animal Models for Cerebrovascular Disorders
Vascular Disease Prevention (Discontinued) Editorial [Progress of “Current Alzheimer Research” and Future Direction]
Current Alzheimer Research Biology of Subjective Cognitive Complaint Amongst Geriatric Patients: Vitamin D Involvement
Current Alzheimer Research G Protein-Coupled Receptors: Target-Based In Silico Screening
Current Pharmaceutical Design MicroRNA Expression Analysis of Adult-Onset Drosophila Alzheimer`s Disease Model
Current Alzheimer Research Dietary Fat Intake and Risk of Alzheimer’s Disease and Dementia: A Meta-Analysis of Cohort Studies
Current Alzheimer Research Cushing's Syndrome and Steroid Dementia
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery CSF as a Surrogate for Assessing CNS Exposure: An Industrial Perspective
Current Drug Metabolism Exosomes and Exosomal microRNAs in Age-associated Stroke
Current Vascular Pharmacology Transgenic Mouse Models of Parkinsons Disease and Huntingtons Disease
CNS & Neurological Disorders - Drug Targets The Predictive Value of Lipid Markers in Vascular Disease
Current Pharmaceutical Design Advances in Drug Delivery from Nose to Brain: An Overview
Current Drug Therapy A Predictive Model of the Prevalence of Delirium in Elderly Subjects Admitted to Nursing Homes
Endocrine, Metabolic & Immune Disorders - Drug Targets Transgenic C. elegans as a Model in Alzheimers Research
Current Alzheimer Research Comparative Effectiveness of Agmatine and Choline Treatment in Rats with Cognitive Impairment Induced by AlCl<sub>3</sub> and Forced Swim Stress
Current Clinical Pharmacology Multitarget Therapeutic Effect of Fasudil in APP/PS1transgenic Mice
CNS & Neurological Disorders - Drug Targets Large-Scale Prediction of Drug Targets Based on Local and Global Consistency of Chemical-Chemical Networks
Combinatorial Chemistry & High Throughput Screening The Potential Role of Sirtuins Regarding the Effects of Exercise on Aging- Related Diseases
Current Aging Science