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
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
-
Applications of Human Umbilical Cord Blood Cells in Central Nervous System Regeneration
Current Stem Cell Research & Therapy Acetate Suppresses Lipopolysaccharide-stimulated Nitric Oxide Production in Primary Rat Microglia but not in BV-2 Microglia Cells
Current Molecular Pharmacology Rectifying Attenuated Store-Operated Calcium Entry as a Therapeutic Approach for Alzheimer’s Disease
Current Alzheimer Research Recent Approaches for Studying the Role of Glia
CNS & Neurological Disorders - Drug Targets Ghrelin as a Neuroprotective and Palliative Agent in Alzheimer's and Parkinson's Disease
Current Pharmaceutical Design Alteration of Isocitrate Dehydrogenase Following Acute Ischemic Injury as a Means to Improve Cellular Energetic Status in Neuroadaptation
CNS & Neurological Disorders - Drug Targets SS31, a Small Molecule Antioxidant Peptide, Attenuates β-Amyloid Elevation, Mitochondrial/Synaptic Deterioration and Cognitive Deficit in SAMP8 Mice
Current Alzheimer Research Anti-Amyloidogenic and Anti-Apoptotic Role of Melatonin in Alzheimer Disease
Current Neuropharmacology Redox Processes in Neurodegenerative Disease Involving Reactive Oxygen Species
Current Neuropharmacology Meet the Editorial Board:
Current Medicinal Chemistry PET Measurements of cAMP-Mediated Phosphodiesterase-4 with (R)-[11C]Rolipram
Current Radiopharmaceuticals Tacrine Derivatives and Alzheimers Disease
Current Medicinal Chemistry Physical Exercise for the Treatment of Neuropsychiatric Disturbances in Alzheimer’s Dementia: Possible Mechanisms, Current Evidence and Future Directions
Current Alzheimer Research Targeting Cancer and Neuropathy with Histone Deacetylase Inhibitors:Two Birds with One Stone?
Current Cancer Drug Targets Position Based Nucleotide Analysis of miR168 Family in Higher Plants and its Targets in Mammalian Transcripts
MicroRNA New Therapeutic Property of Dimebon as a Neuroprotective Agent
Current Medicinal Chemistry Multivalent & Multifunctional Ligands to β-Amyloid
Current Pharmaceutical Design Changes in Peripheral Blood Biomarkers with Aging and Neurodegenerative Disorders
Current Aging Science Age-Related Neurodegeneration Prevention Through mTOR Inhibition: Potential Mechanisms and Remaining Questions
Current Topics in Medicinal Chemistry A Role for TGF-β Signaling in Neurodegeneration: Evidence from Genetically Engineered Models
Current Alzheimer Research