Abstract
α-Synuclein is a small neuronal protein that has been implicated to play an important role in Parkinsons disease. Genetic mutations and multiplications in the α-synuclein gene can cause familial forms of the disease. In aggregated fibrillar form, α-synuclein is the main component of Lewy bodies, the intraneuronal inclusion bodies characteristic of Parkinsons disease. The loss of functional dopaminergic neurons in Parkinsons disease may be caused by a gain in toxic function of the protein. Elucidating if this gain of toxic function is related to the aggregation of α-synuclein may be vital in understanding Parkinsons disease. Although there are many ideas on how α-synuclein could be involved in the disease, this review will focus on the amyloid pore hypothesis. This hypothesis assumes that aggregation intermediates or oligomers are more likely to be toxic than monomeric or fibrillar forms of the protein. Oligomeric species are thought to exercise their toxicity through permeabilization of cellular membranes. Membrane pore formation by an oligomeric intermediate might play a role in other neurodegenerative disorders in which protein aggregation and amyloid formation play a role, such as Alzheimers disease. We will discuss the role of this hypothesis in Parkinsons disease.
Keywords: α-Synuclein, amyloid, disruption, membrane, oligomer, Parkinson's disease, permeabilization, pore
Current Protein & Peptide Science
Title: Membrane Interactions of Oligomeric Alpha-Synuclein: Potential Role in Parkinsons Disease
Volume: 11 Issue: 5
Author(s): Bart D. van Rooijen, Mireille M.A.E. Claessens and Vinod Subramaniam
Affiliation:
Keywords: α-Synuclein, amyloid, disruption, membrane, oligomer, Parkinson's disease, permeabilization, pore
Abstract: α-Synuclein is a small neuronal protein that has been implicated to play an important role in Parkinsons disease. Genetic mutations and multiplications in the α-synuclein gene can cause familial forms of the disease. In aggregated fibrillar form, α-synuclein is the main component of Lewy bodies, the intraneuronal inclusion bodies characteristic of Parkinsons disease. The loss of functional dopaminergic neurons in Parkinsons disease may be caused by a gain in toxic function of the protein. Elucidating if this gain of toxic function is related to the aggregation of α-synuclein may be vital in understanding Parkinsons disease. Although there are many ideas on how α-synuclein could be involved in the disease, this review will focus on the amyloid pore hypothesis. This hypothesis assumes that aggregation intermediates or oligomers are more likely to be toxic than monomeric or fibrillar forms of the protein. Oligomeric species are thought to exercise their toxicity through permeabilization of cellular membranes. Membrane pore formation by an oligomeric intermediate might play a role in other neurodegenerative disorders in which protein aggregation and amyloid formation play a role, such as Alzheimers disease. We will discuss the role of this hypothesis in Parkinsons disease.
Export Options
About this article
Cite this article as:
D. van Rooijen Bart, M.A.E. Claessens Mireille and Subramaniam Vinod, Membrane Interactions of Oligomeric Alpha-Synuclein: Potential Role in Parkinsons Disease, Current Protein & Peptide Science 2010; 11 (5) . https://dx.doi.org/10.2174/138920310791330659
DOI https://dx.doi.org/10.2174/138920310791330659 |
Print ISSN 1389-2037 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5550 |
Call for Papers in Thematic Issues
Advancements in Proteomic and Peptidomic Approaches in Cancer Immunotherapy: Unveiling the Immune Microenvironment
The scope of this thematic issue centers on the integration of proteomic and peptidomic technologies into the field of cancer immunotherapy, with a particular emphasis on exploring the tumor immune microenvironment. This issue aims to gather contributions that illustrate the application of these advanced methodologies in unveiling the complex interplay ...read more
Artificial Intelligence for Protein Research
Protein research, essential for understanding biological processes and creating therapeutics, faces challenges due to the intricate nature of protein structures and functions. Traditional methods are limited in exploring the vast protein sequence space efficiently. Artificial intelligence (AI) and machine learning (ML) offer promising solutions by improving predictions and speeding up ...read more
Nutrition and Metabolism in Musculoskeletal Diseases
The musculoskeletal system consists mainly of cartilage, bone, muscles, tendons, connective tissue and ligaments. Balanced metabolism is of vital importance for the homeostasis of the musculoskeletal system. A series of musculoskeletal diseases (for example, sarcopenia, osteoporosis) are resulted from the dysregulated metabolism of the musculoskeletal system. Furthermore, metabolic diseases (such ...read more
Protein Folding, Aggregation and Liquid-Liquid Phase Separation
Protein folding, misfolding and aggregation remain one of the main problems of interdisciplinary science not only because many questions are still open, but also because they are important from the point of view of practical application. Protein aggregation and formation of fibrillar structures, for example, is a hallmark of a ...read more
Related Journals
- 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
Related Articles
-
Introduction: Strategies, Molecular Targets and Animal Models Useful for Developing Therapies for Alzheimers Disease
Current Medicinal Chemistry - Central Nervous System Agents ES-MDA: Enhanced Similarity-based MiRNA-Disease Association
Current Protein & Peptide Science Down-Regulation of Mir-107 Worsen Spatial Memory by Suppressing SYK Expression and Inactivating NF-ΚB Signaling Pathway
Current Alzheimer Research Current Research on Opioid Receptor Function
Current Drug Targets State Dissociation, Human Behavior, and Consciousness
Current Topics in Medicinal Chemistry Bee Venom: Its Potential Use in Alternative Medicine
Anti-Infective Agents miRNAs in Alzheimer Disease – A Therapeutic Perspective
Current Alzheimer Research Phosphodiesterase: An Interface Connecting Cognitive Deficits to Neuropsychiatric and Neurodegenerative Diseases
Current Pharmaceutical Design Novel Target Sites for Drug Screening: A Special Reference to Cancer, Rheumatoid Arthritis and Parkinson’s Disease
Current Signal Transduction Therapy Genetic Bases of Progressive Supranuclear Palsy: The MAPT Tau Disease
Current Medicinal Chemistry Preface: A New Era of Nanoimmunology
Current Pharmaceutical Biotechnology Insights into the Structure, Function, and Regulation of Human Cytochrome P450 1A2
Current Drug Metabolism The Complex Actions of Statins in Brain and their Relevance for Alzheimer`s Disease Treatment: An Analytical Review
Current Alzheimer Research Pituitary Adenylate Cyclase-Activating Polypeptide: Focus on Structure- Activity Relationships of a Neuroprotective Peptide
Current Medicinal Chemistry Conantokins Inhibitors of Ion Flow through the N-Methyl-D-Aspartate Receptor Channels
Current Drug Targets A Systematic Review on Donepezil-based Derivatives as Potential Cholinesterase Inhibitors for Alzheimer’s Disease
Current Medicinal Chemistry Gene Therapy and Cell Reprogramming For the Aging Brain: Achievements and Promise
Current Gene Therapy Phosphatidylserine and Curcumin Act Synergistically to Down-Regulate Release of Interleukin-1β from Lipopolysaccharide-Stimulated Cortical Primary Microglial Cells
CNS & Neurological Disorders - Drug Targets Amyloidogenesis of Natively Unfolded Proteins
Current Alzheimer Research Good Epidemiologic Practice in Retinitis Pigmentosa: From Phenotyping to Biobanking
Current Genomics