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
-
Bridging Over the Troubled Heterogeneity of SPG-Related Pathologies: Mechanisms Unite What Genetics Divide
Current Molecular Medicine Structural Changes in Alzheimers Disease Brain Microvessels
Current Alzheimer Research Dimebon Attenuates the Aβ-Induced Mitochondrial Permeabilization
Current Alzheimer Research Functional Neuroanatomy of the Noradrenergic Locus Coeruleus: Its Roles in the Regulation of Arousal and Autonomic Function Part II: Physiological and Pharmacological Manipulations and Pathological Alterations of Locus Coeruleus Activity in Humans
Current Neuropharmacology Benzimidazole Derivatives as Centerally Acting Agents
Current Drug Therapy CD14-Dependent Innate Immunity-Mediated Neuronal Damage in Vivo is Suppressed by NSAIDs and Ablation of a Prostaglandin E2 Receptor, EP2
Current Medicinal Chemistry - Central Nervous System Agents Ginsenoside Rg1 Attenuates Oligomeric Aβ1-42-Induced Mitochondrial Dysfunction
Current Alzheimer Research Expression and Function of the Endocannabinoid System in Glial Cells
Current Pharmaceutical Design The Proinflammatory Cytokine GITRL Contributes to TRAIL-mediated Neurotoxicity in the HCN-2 Human Neuronal Cell Line
Current Alzheimer Research Use of Deoxyribozymes for Gene Knockdown
Medicinal Chemistry Reviews - Online (Discontinued) Avoidance of Aβ[25-35] / (H2O2) -Induced Apoptosis in Lymphocytes by the Cannabinoid Agonists CP55, 940 and JWH-015 via Receptor-Independent and PI3K-Dependent Mechanisms: Role of NF- κB and p53
Medicinal Chemistry Targeting Tumor Necrosis Factor Alpha for Alzheimer’s Disease
Current Alzheimer Research Single Amino Acid Repeats Connect Viruses to Neurodegeneration
Current Drug Discovery Technologies Dissecting the Biological Effects of Isoflurane through the Mechanistic Target of Rapamycin (mTOR) and microRNAs (miRNAs)
Current Neurovascular Research Clinical Trials for Neuroprotection in ALS
CNS & Neurological Disorders - Drug Targets Ureas: Applications in Drug Design
Current Medicinal Chemistry Patent Selections
Recent Patents on Biotechnology The Multiple Pharmaceutical Potential of Curcumin in Parkinson's Disease
CNS & Neurological Disorders - Drug Targets Preface:
Current Topics in Medicinal Chemistry Predementia and Dementia Syndromes: Possible Role of Lipoprotein Metabolism
Vascular Disease Prevention (Discontinued)