Abstract
A number of studies have demonstrated a role for transition metals and oxidative stress in the etiology of Parkinson ’ s disease (PD). Genetic and biochemical evidence also clearly links the protein alpha-synuclein (αSyn) to PD and a number of associated diseases. In these “synucleinopathies”, αSyn is deposited, often in oligomerized forms, as cytoplasmic inclusions known as Lewy bodies and Lewy neurites. αSyn cross-linking/oligomerization can occur via a number of processes, most stimulated by metal catalyzed oxidation (MCO). In PD, the increased sensitivity of midbrain neurons expressing high levels of oxidizable catecholamines may provide one clue to account for degeneration of these neurons. In other regions of the nervous system that develop Lewy body pathology, the mode of αSyn oligomerization is less clear. Thus, the relationship between αSyn and MCO, either direct or indirect, represents a particular concern for possible treatment of these various diseases.
Keywords: Parkinson's disease, alpha-synuclein, metals, oxidation, dopamine, oligomerization, cross-linking, neuromelanin
Current Alzheimer Research
Title: Metal Catalyzed Oxidation of Alpha-Synuclein – A Role for Oligomerization in Pathology?
Volume: 5 Issue: 6
Author(s): N. B. Cole
Affiliation:
Keywords: Parkinson's disease, alpha-synuclein, metals, oxidation, dopamine, oligomerization, cross-linking, neuromelanin
Abstract: A number of studies have demonstrated a role for transition metals and oxidative stress in the etiology of Parkinson ’ s disease (PD). Genetic and biochemical evidence also clearly links the protein alpha-synuclein (αSyn) to PD and a number of associated diseases. In these “synucleinopathies”, αSyn is deposited, often in oligomerized forms, as cytoplasmic inclusions known as Lewy bodies and Lewy neurites. αSyn cross-linking/oligomerization can occur via a number of processes, most stimulated by metal catalyzed oxidation (MCO). In PD, the increased sensitivity of midbrain neurons expressing high levels of oxidizable catecholamines may provide one clue to account for degeneration of these neurons. In other regions of the nervous system that develop Lewy body pathology, the mode of αSyn oligomerization is less clear. Thus, the relationship between αSyn and MCO, either direct or indirect, represents a particular concern for possible treatment of these various diseases.
Export Options
About this article
Cite this article as:
Cole B. N., Metal Catalyzed Oxidation of Alpha-Synuclein – A Role for Oligomerization in Pathology?, Current Alzheimer Research 2008; 5 (6) . https://dx.doi.org/10.2174/156720508786898523
DOI https://dx.doi.org/10.2174/156720508786898523 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
Call for Papers in Thematic Issues
New Advances in the Prevention, Diagnosis, Treatment, and Rehabilitation of Alzheimer's Disease
Aims and Scope: Introduction: Alzheimer's disease (AD) poses a significant global health challenge, with an increasing prevalence that demands concerted efforts to advance our understanding and strategies for prevention, diagnosis, treatment, and rehabilitation. This thematic issue aims to bring together cutting-edge research and innovative approaches from multidisciplinary perspectives to address ...read more
Current updates on the Role of Neuroinflammation in Neurodegenerative Disorders
Neuroinflammation is an invariable hallmark of chronic and acute neurodegenerative disorders and has long been considered a potential drug target for Alzheimer?s disease (AD) and dementia. Significant evidence of inflammatory processes as a feature of AD is provided by the presence of inflammatory markers in plasma, CSF and postmortem brain ...read more
Deep Learning for Advancing Alzheimer's Disease Research
Alzheimer's disease (AD) poses a significant global health challenge, with an increasing number of individuals affected yearly. Deep learning, a subfield of artificial intelligence, has shown immense potential in various domains, including healthcare. This thematic issue of Current Alzheimer Research explores the application of deep learning techniques in advancing our ...read more
Diagnostic and therapeutic biomarkers of dementia
Dementia affects 18 million people worldwide. Dementia is a syndrome of symptoms caused by brain disease, usually chronic or progressive, clinically characterized by multiple impairments of higher cortical functions such as memory, thinking, orientation, and learning. In addition, in the course of dementia, cognitive deficits are observed, which often hinder ...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
-
Synthetic Routes and Biological Activities of Benzofuran and its Derivatives: A Review
Letters in Organic Chemistry Cdc25A Protein Phosphatase: A Therapeutic Target for Liver Cancer Therapies
Anti-Cancer Agents in Medicinal Chemistry Copper and Heme-Mediated Abeta Toxicity: Redox Chemistry, Abeta Oxidations and Anti-ROS Compounds
Current Topics in Medicinal Chemistry Resveratrol and Its Analogues: Promising Antitumor Agents
Anti-Cancer Agents in Medicinal Chemistry Cell-Selective Mitochondrial Targeting: Progress in Mitochondrial Medicine
Current Drug Delivery Cultured Adult Animal Neurons and Schwann Cells Give Us New Insights into Diabetic Neuropathy
Current Diabetes Reviews Extracellular ATP and Neurodegeneration
Current Drug Targets - CNS & Neurological Disorders Activities of Venom Proteins and Peptides with Possible Therapeutic Applications from Bees and WASPS
Protein & Peptide Letters Exploring Protein-Protein Interactions with Synthetic Peptide Arrays
Mini-Reviews in Organic Chemistry Improving Cancer Chemotherapy with Modulators of ABC Drug Transporters
Current Drug Targets A hypothesis for the role of RECK in angiogenesis
Current Vascular Pharmacology Co-Treatment With Copper Compounds Dramatically Decreases Toxicities Observed With Cisplatin Cancer Therapy And The Anticancer Efficacy Of Some Copper Chelates Supports The Conclusion That Copper Chelate Therapy May Be Markedly More Effective And Less Toxic Than Cisplatin Therapy
Current Medicinal Chemistry Epigenetic Regulation of ABCB1 Transporter Expression and Function
Current Pharmacogenomics and Personalized Medicine DNA Double Strand Breaks: A Common Theme in Neurodegenerative Diseases
Current Alzheimer Research The Killing of Human Neuroblastoma Cells by the Small Molecule JQ1 Occurs in a p53-Dependent Manner
Anti-Cancer Agents in Medicinal Chemistry Multifunctional Role of Pacap-Like Peptides in Molluscs
Protein & Peptide Letters Does Parkinson’s Disease and Type-2 Diabetes Mellitus Present Common Pathophysiological Mechanisms and Treatments?
CNS & Neurological Disorders - Drug Targets Structure-Function Relationships of Antimicrobial Peptides and Proteins with Respect to Contact Molecules on Pathogen Surfaces
Current Topics in Medicinal Chemistry Medicinal Value and Potential Therapeutic Mechanisms of Gynostemma pentaphyllum (Thunb.) Makino and Its Derivatives: An Overview
Current Topics in Medicinal Chemistry Endocannabinoid Signaling in Midbrain Dopamine Neurons: More than Physiology?
Current Neuropharmacology