Abstract
The misfolding of proteins into a toxic conformation is proposed to be at the molecular foundation of a number of neurodegenerative disorders including Alzheimers and Parkinsons diseases. Evidence that α-synuclein amyloidogenesis plays a causative role in the development of Parkinsons disease is furnished by a variety of genetic, neuropathological and biochemical studies. There is a major interest in understanding the structural and toxicity features of the various species populated along the aggregation pathway of this protein. The development of multidimensional Nuclear Magnetic Resonance (NMR) spectroscopy in liquid and solid state over the last decade has significantly increased the scope of molecules that are amenable for structural studies. The aim of this review is to provide a picture of how NMR tools were used in concert to decipher the structural and dynamic properties of the intrinsically disordered protein α- synuclein in its native, oligomeric, fibril and membrane-bound states. Understanding the structural and molecular basis behind the aggregation pathway of α-synuclein is key to advance in the design of a therapeutic strategy.
Keywords: Amyloid, intrinsically disordered proteins, NMR spectroscopy, Parkinson's disease, structural biology, Amyloid Aggregation, α-Synuclein, toxic conformation, Alzheimer's disease, Neurodegenerative Diseases, fibril morphology
Current Protein & Peptide Science
Title: Structures Behind the Amyloid Aggregation of α-Synuclein: An NMR based Approach
Volume: 12 Issue: 3
Author(s): Maria L. Orcellet and Claudio O. Fernandez
Affiliation:
Keywords: Amyloid, intrinsically disordered proteins, NMR spectroscopy, Parkinson's disease, structural biology, Amyloid Aggregation, α-Synuclein, toxic conformation, Alzheimer's disease, Neurodegenerative Diseases, fibril morphology
Abstract: The misfolding of proteins into a toxic conformation is proposed to be at the molecular foundation of a number of neurodegenerative disorders including Alzheimers and Parkinsons diseases. Evidence that α-synuclein amyloidogenesis plays a causative role in the development of Parkinsons disease is furnished by a variety of genetic, neuropathological and biochemical studies. There is a major interest in understanding the structural and toxicity features of the various species populated along the aggregation pathway of this protein. The development of multidimensional Nuclear Magnetic Resonance (NMR) spectroscopy in liquid and solid state over the last decade has significantly increased the scope of molecules that are amenable for structural studies. The aim of this review is to provide a picture of how NMR tools were used in concert to decipher the structural and dynamic properties of the intrinsically disordered protein α- synuclein in its native, oligomeric, fibril and membrane-bound states. Understanding the structural and molecular basis behind the aggregation pathway of α-synuclein is key to advance in the design of a therapeutic strategy.
Export Options
About this article
Cite this article as:
L. Orcellet Maria and O. Fernandez Claudio, Structures Behind the Amyloid Aggregation of α-Synuclein: An NMR based Approach, Current Protein & Peptide Science 2011; 12 (3) . https://dx.doi.org/10.2174/138920311795860160
DOI https://dx.doi.org/10.2174/138920311795860160 |
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
-
Syntheses of Ethyl Pyruvate’s Bioisosteres Inhibiting Inducible Nitric Oxide Production in Lipopolysaccharide-induced BV2 Cells
Letters in Drug Design & Discovery Efficacy and Toxicity of Clioquinol Treatment and A-beta42 Inoculation in the APP/PSI Mouse Model of Alzheimer's Disease
Current Alzheimer Research S100b Induces Expression of Myoglobin in APβ Treated Neuronal Cells In Vitro: A Possible Neuroprotective Mechanism
Current Aging Science Is Brain-Derived Neurotrophic Factor: A Common Link Between Neurodegenerative Disorders and Cancer?
Current Alzheimer Research Decline of Executive Processes Affects the Identification of Emotional Facial Expressions in Aging
Current Aging Science The Role of Peroxidation of Mitochondrial Membrane Phospholipids in Pancreatic β -Cell Failure
Current Diabetes Reviews The Glutamatergic Neurotransmission in the Central Nervous System
Current Medicinal Chemistry Chemical Diversity of Grape Products, a Complex Blend of Bioactive Secondary Metabolites
The Natural Products Journal Is there a Rational Approach for Increasing Drug Specificity? Considerations on CNS Target Choice and Validation
Recent Patents on CNS Drug Discovery (Discontinued) Tau Silencing by siRNA in the P301S Mouse Model of Tauopathy
Current Gene Therapy Targeting TRPs in Neurodegenerative Disorders
Current Topics in Medicinal Chemistry When is a Proof-of-Concept (POC) not a POC? Pomaglumetad (LY2140023) as a Case Study for Antipsychotic Efficacy
Current Pharmaceutical Design The Role of Extracellular Adenosine in Chemical Neurotransmission in the Hippocampus and Basal Ganglia: Pharmacological and Clinical Aspects
Current Topics in Medicinal Chemistry Editorial (How Natural is it for Nature to Help with Major Depressive Disorder?)
CNS & Neurological Disorders - Drug Targets Minocycline: Neuroprotective Mechanisms in Parkinsons Disease
Current Pharmaceutical Design Salidroside - Can it be a Multifunctional Drug?
Current Drug Metabolism Gene Therapy and Cell Reprogramming For the Aging Brain: Achievements and Promise
Current Gene Therapy Tuning and Fine-Tuning of Synapses with Adenosine
Current Neuropharmacology Neuroinflammation: A Therapeutic Target of Cotinine for the Treatment of Psychiatric Disorders?
Current Pharmaceutical Design Vascular Endothelial Growth Factor: Adaptive Changes in the Neuroglialvascular Unit
Current Neurovascular Research