Abstract
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the death of motor neurons. About 10% of ALS cases are inherited (familial), and a large subset of them are caused by mutations in the gene encoding the copper-zinc superoxide dismutase (SOD1). The detection of SOD1-positive inclusions in familial ALS patients suggests the role of SOD1 aggregation underlying the pathology of familial ALS. Although SOD1 mutant proteins are different in structure, stability and activity, they all exhibit a higher aggregation propensity than wild-type SOD1. We here review the recent studies on the role of metallation states and disulfide status in the unfolding, misfolding, and aggregation of SOD1. Investigations of the mechanism of SOD1 aggregation enhance our understanding of onset and progression of ALS and have implications for therapeutic approaches for treating ALS.
Keywords: Amyotrophic lateral sclerosis, copper-zinc superoxide dismutase, protein aggregation, metallation state, disulfide status.
Current Topics in Medicinal Chemistry
Title:SOD1 Aggregation and ALS: Role of Metallation States and Disulfide Status
Volume: 12 Issue: 22
Author(s): Yuewei Sheng, Madhuri Chattopadhyay, Julian Whitelegge and Joan Selverstone Valentine
Affiliation:
Keywords: Amyotrophic lateral sclerosis, copper-zinc superoxide dismutase, protein aggregation, metallation state, disulfide status.
Abstract: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the death of motor neurons. About 10% of ALS cases are inherited (familial), and a large subset of them are caused by mutations in the gene encoding the copper-zinc superoxide dismutase (SOD1). The detection of SOD1-positive inclusions in familial ALS patients suggests the role of SOD1 aggregation underlying the pathology of familial ALS. Although SOD1 mutant proteins are different in structure, stability and activity, they all exhibit a higher aggregation propensity than wild-type SOD1. We here review the recent studies on the role of metallation states and disulfide status in the unfolding, misfolding, and aggregation of SOD1. Investigations of the mechanism of SOD1 aggregation enhance our understanding of onset and progression of ALS and have implications for therapeutic approaches for treating ALS.
Export Options
About this article
Cite this article as:
Sheng Yuewei, Chattopadhyay Madhuri, Whitelegge Julian and Selverstone Valentine Joan, SOD1 Aggregation and ALS: Role of Metallation States and Disulfide Status, Current Topics in Medicinal Chemistry 2012; 12 (22) . https://dx.doi.org/10.2174/1568026611212220010
DOI https://dx.doi.org/10.2174/1568026611212220010 |
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
-
Mitochondria as a Therapeutic Target for Aging and Neurodegenerative Diseases
Current Alzheimer Research Neuron-Microglia Interaction in Neuroinflammation
Current Protein & Peptide Science Role of Sirtuins and Calorie Restriction in Neuroprotection: Implications in Alzheimers and Parkinsons Diseases
Current Pharmaceutical Design Editorial [Hot Topic: Advances in Alzheimer Therapy: Development of Innovative New Strategies (Guest Editors: Nigel H. Greig, Ezio Giacobini and Debomoy K. Lahiri)]
Current Alzheimer Research Alzheimer´s Disease and Oxidative Stress: A Review
Current Medicinal Chemistry A Comprehensive Review of Alzheimer’s Association with Related Proteins: Pathological Role and Therapeutic Significance
Current Neuropharmacology Insights into the Mechanism of the Therapeutic Potential of Herbal Monoamine Oxidase Inhibitors in Neurological Diseases
Current Drug Targets P-gp Transporter and its Role in Neurodegenerative Diseases
Current Topics in Medicinal Chemistry Therapeutic Targets in Extracellular Protein Deposition Diseases
Current Medicinal Chemistry Short-Term Ultramicronized Palmitoylethanolamide Therapy in Patients with Myasthenia Gravis: a Pilot Study to Possible Future Implications of Treatment
CNS & Neurological Disorders - Drug Targets Protein Kinases and their Modulation in the Central Nervous System
Current Medicinal Chemistry - Central Nervous System Agents Inflammatory Cyclooxygenase Activity and PGE<sub>2</sub> Signaling in Models of Alzheimer’s Disease
Current Immunology Reviews (Discontinued) Erythropoietin: A Neuroprotective Agent in Cerebral Hypoxia, Neurodegeneration, and Epilepsy
Current Pharmaceutical Design Oxidative Stress and Neurodegenerative Diseases: A Review of Upstream and Downstream Antioxidant Therapeutic Options
Current Neuropharmacology Neuroprotective Effects of Tetracyclines: Molecular Targets, Animal Models and Human Disease
CNS & Neurological Disorders - Drug Targets Coenzyme Q10 in Neuromuscular and Neurodegenerative Disorders
Current Drug Targets Small Molecules Activating TrkB Receptor for Treating a Variety of CNS Disorders
CNS & Neurological Disorders - Drug Targets Endocannabinoid Receptors in the CNS: Potential Drug Targets for the Prevention and Treatment of Neurologic and Psychiatric Disorders
Current Neuropharmacology NAD Precursors, Mitochondria Targeting Compounds and ADP-Ribosylation Inhibitors in Treatment of Inflammatory Diseases and Cancer
Current Medicinal Chemistry Chromosome 17 in Fronto Temporal Lobak Degeneration (FTLD): From MAPT to Progranulin and Back
Current Alzheimer Research