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
-
The Double Roles of the Prostaglandin E<sub>2</sub> EP2 Receptor in Intracerebral Hemorrhage
Current Drug Targets <i>In Silico</i> Insight into the Inhibitory Effects of Active Antidiabetic Compounds from Medicinal Plants Against SARS-CoV-2 Replication and Posttranslational Modification
Coronaviruses Structural Properties of the NMDA Receptor and the Design of Neuroprotective Therapies
Mini-Reviews in Medicinal Chemistry Glucose Blood Levels as a Therapeutic Target in Acute Ischaemic Stroke Setting
Current Topics in Medicinal Chemistry Meet Our Editorial Board Member
Current Pharmaceutical Design Activation of Brain Endothelium by Soluble Aggregates of the Amyloid-β Protein Involves Nuclear Factor-κB
Current Alzheimer Research Redox Signaling Pathways Involved in Neuronal Ischemic Preconditioning
Current Neuropharmacology Selecting Good ‘Drug-Like’ Properties to Optimize Small Molecule Blood-Brain Barrier Penetration
Current Medicinal Chemistry Oxidative RNA Damage and Neurodegeneration
Current Medicinal Chemistry Systematic Evaluation of Drug-Loaded Hydrogels for Application in Osteosarcoma Treatment
Current Pharmaceutical Biotechnology Targeting the Alpha 7 Nicotinic Acetylcholine Receptor to Reduce Amyloid Accumulation in Alzheimers Disease Pyramidal Neurons
Current Pharmaceutical Design Hypoxia as an Initiator of Neuroinflammation: Microglial Connections
Current Neuropharmacology Stimuli-Responsive Nanocarriers for Drug Delivery to the Central Nervous System
Current Nanoscience Role of Curcumin in Regulation of TNF-α Mediated Brain Inflammatory Responses
Recent Patents on Inflammation & Allergy Drug Discovery From Biomarkers to Cytokine-like Hormones: Uncovering New Directives for Cognitive Loss and Alzheimer’s Disease
Current Neurovascular Research Chronic Stress Impacts on Olfactory System
CNS & Neurological Disorders - Drug Targets Natural Compounds Therapeutic Features in Brain Disorders by Experimental, Bioinformatics and Cheminformatics Methods
Current Medicinal Chemistry PET Imaging of the Peripheral Benzodiazepine Receptor: Monitoring Disease Progression and Therapy Response in Neurodegenerative Disorders
Current Pharmaceutical Design Application of Glutathione as Anti-Oxidative and Anti-Aging Drugs
Current Drug Metabolism Mitochondrial Serine Protease HtrA2/Omi as a Potential Therapeutic Target
Current Drug Targets