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
AlphaFold in Medicinal Chemistry: Opportunities and Challenges
AlphaFold, a groundbreaking AI tool for protein structure prediction, is revolutionizing drug discovery. Its near-atomic accuracy unlocks new avenues for designing targeted drugs and performing efficient virtual screening. However, AlphaFold's static predictions lack the dynamic nature of proteins, crucial for understanding drug action. This is especially true for multi-domain proteins, ...read more
Artificial intelligence for Natural Products Discovery and Development
Our approach involves using computational methods to predict the potential therapeutic benefits of natural products by considering factors such as drug structure, targets, and interactions. We also employ multitarget analysis to understand the role of drug targets in disease pathways. We advocate for the use of artificial intelligence in predicting ...read more
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
Chronic Kidney Disease
The scope of the special thematic issue includes but not limited to the mechanism of chronic kidney disease (CKD), the treatment of renal fibrosis and early diagnosis of CKD and so on. We also welcome manuscripts from other scientific research area with respect to internal medicine. Cell death has been ...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
-
Integration of <sup>18</sup>FDG-PET Metabolic and Functional Connectomes in the Early Diagnosis and Prognosis of the Alzheimer's Disease
Current Alzheimer Research Tanshinone IIA: Pharmacology, Total Synthesis, and Progress in Structure-modifications
Current Medicinal Chemistry Sulfur – Containing Amino Acids in Seizures: Current State of the Art
Current Medicinal Chemistry “Tripping out” with the TRP Superfamily and TRPV1 for Novel Neuroprotection
Current Neurovascular Research Midkine: A Promising Molecule for Drug Development to Treat Diseases of the Central Nervous System
Current Pharmaceutical Design The Role of P-Glycoprotein in Psychiatric Disorders: A Reliable Guard of the Brain?
Central Nervous System Agents in Medicinal Chemistry The Impact of Working Memory Training on Cognitive Abilities in Older Adults: The Role of Cognitive Reserve
Current Aging Science The Effects of Different Antioxidants on the Activity of Cerebrocortical MnSOD and Na,K-ATPase from post mortem Alzheimer’s Disease and Age-matched Normal Brains
Current Alzheimer Research Glucose Control and Use of Continuous Glucose Monitoring in the Intensive Care Unit: A Critical Review
Current Diabetes Reviews The Regulation of Brain Nucleoside Utilization
Current Metabolomics The Prevalence, Morbidities, and Treatments of Insomnia
CNS & Neurological Disorders - Drug Targets Nonbacterial Thrombotic Endocarditis (Marantic Endocarditis) in Cancer Patients
Cardiovascular & Hematological Disorders-Drug Targets UGT1A1 Mediated Drug Interactions and its Clinical Relevance
Current Drug Metabolism Changes in the Expression of the Alzheimers Disease-Associated Presenilin Gene in Drosophila Heart Leads to Cardiac Dysfunction
Current Alzheimer Research Depression has a Strong Relationship to Alterations in the Immune, Endocrine and Neural System
Current Psychiatry Reviews Urinary Metabolomics Reveals Alterations of Aromatic Amino Acid Metabolism of Alzheimer’s Disease in the Transgenic CRND8 Mice
Current Alzheimer Research Hydrophobic Plant Antioxidants. Preparation of Nanoparticles and their Application for Prevention of Neurodegenerative Diseases. Review and Experimental Data
Current Topics in Medicinal Chemistry Advances and Patents about Medical Surgical Operation Bone Drilling Equipment
Recent Patents on Mechanical Engineering NMDA-antagonism (Memantine): An Alternative Pharmacological Therapeutic Principle in Alzheimers and Vascular Dementia
Current Pharmaceutical Design Biochemical Properties of Indoleamine 2,3-dioxygenase: From Structure to Optimized Design of Inhibitors
Current Medicinal Chemistry