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
-
Chronic Diseases and COVID-19: A Review
Endocrine, Metabolic & Immune Disorders - Drug Targets Lysosomal Modulatory Drugs for a Broad Strategy Against Protein Accumulation Disorders
Current Alzheimer Research Proposing a “Lipemic Index” As a Nutritional and Research Tool
Current Vascular Pharmacology Editorial (Thematic Issue: Current and Perspective Therapeutic Strategies for Alzheimer's Disease)
Current Pharmaceutical Design Induction of Serine Racemase Expression and D-Serine Release from Microglia by Secreted Amyloid Precursor Protein (sAPP)
Current Alzheimer Research Fetal Programming of the Human Brain: Is there a Link with Insurgence of Neurodegenerative Disorders in Adulthood?
Current Medicinal Chemistry Inhalational Injury: A Brief Review of Pathophysiology, Diagnosis and Treatment
Current Respiratory Medicine Reviews Niacin Status, NAD Distribution and ADP-Ribose Metabolism
Current Pharmaceutical Design Association between ALDH2 Gene Polymorphism and Late-onset Alzheimer Disease: An Up-to-date Meta-analysis
Current Alzheimer Research Parkinsons Disease Dementia
Current Psychiatry Reviews The Malignant Obesity Hypoventilation Syndrome (MOHS)
Current Respiratory Medicine Reviews Current Progress of Reelin in Development, Inflammation and Tissue Remodeling: From Nervous to Visual Systems
Current Molecular Medicine Monitoring Drug Use Among HIV/AIDS Patients in Brazil: Should we Combine Self-Report and Urinalysis?
Current HIV Research Patterns of Cognitive Impairment in Neurological Disease
Current Psychiatry Reviews A New Decision Tree Combining Abeta 1-42 and p-Tau Levels in Alzheimer's Diagnosis
Current Alzheimer Research A Step Further Towards Multitarget Drugs for Alzheimer and Neuronal Vascular Diseases: Targeting the Cholinergic System, Amyloid-β Aggregation and Ca2++ Dyshomeostasis
Current Medicinal Chemistry Reactive Oxygen Species and Antioxidants in the Pathophysiology of Cardiovascular Disease: Does the Actual Knowledge Justify a Clinical Approach?
Current Vascular Pharmacology Therapeutic Targets for the Management of Peripheral Nerve Injury- Induced Neuropathic Pain
CNS & Neurological Disorders - Drug Targets Pharmacogenetics in Geriatric Medicine: Challenges and Opportunities for Clinical Practice
Current Drug Metabolism Hydrogen Sulfide: A New Tool to Design and Develop Drugs
Clinical Anti-Inflammatory & Anti-Allergy Drugs (Discontinued)