Abstract
The past fifteen years have led to a profound re-consideration of the molecular and cellular basis of amyloid diseases. Since the formulation of the amyloid hypothesis in 1991-1992, increasing interest was initially focused at amyloid fibrils and, subsequently, at their precursors, oligomers and pre-fibrillar aggregates as main culprits of cell impairment and demise, particularly in neurodegenerative diseases with amyloid deposition. In 2002, this concept was generalized by the demonstration that pre-fibrillar aggregates were toxic even when they were grown from proteins not associated with amyloid disease. Presently, the general structural features and polymorphism of amyloid fibrils grown from a range of different peptides and proteins are rather well known; however, in spite of the growing interest in amyloid oligomers as the main source of amyloid toxicity, a better definition of their structural features remains elusive due to their transient nature, remarkable instability, high flexibility and structural heterogeneity possibly resulting in the appearance of polymorphic assemblies. Nevertheless, recent studies have started to unravel this key topic by providing significant insights into some general structural features and conformational polymorphism of amyloid oligomers and the higher order structures they generate. Important clues into the structure-toxicity relation of amyloids, the role performed by natural surfaces in oligomer growth and the molecular basis of oligomer-membrane interaction are also emerging.
Keywords: Amyloid, Amyloid oligomer, cytotoxicity, structure, polymorphism, Amyloid fibril
Current Protein & Peptide Science
Title: Structural Polymorphism of Amyloid Oligomers and Fibrils Underlies Different Fibrillization Pathways: Immunogenicity and Cytotoxicity
Volume: 11 Issue: 5
Author(s): Massimo Stefani
Affiliation:
Keywords: Amyloid, Amyloid oligomer, cytotoxicity, structure, polymorphism, Amyloid fibril
Abstract: The past fifteen years have led to a profound re-consideration of the molecular and cellular basis of amyloid diseases. Since the formulation of the amyloid hypothesis in 1991-1992, increasing interest was initially focused at amyloid fibrils and, subsequently, at their precursors, oligomers and pre-fibrillar aggregates as main culprits of cell impairment and demise, particularly in neurodegenerative diseases with amyloid deposition. In 2002, this concept was generalized by the demonstration that pre-fibrillar aggregates were toxic even when they were grown from proteins not associated with amyloid disease. Presently, the general structural features and polymorphism of amyloid fibrils grown from a range of different peptides and proteins are rather well known; however, in spite of the growing interest in amyloid oligomers as the main source of amyloid toxicity, a better definition of their structural features remains elusive due to their transient nature, remarkable instability, high flexibility and structural heterogeneity possibly resulting in the appearance of polymorphic assemblies. Nevertheless, recent studies have started to unravel this key topic by providing significant insights into some general structural features and conformational polymorphism of amyloid oligomers and the higher order structures they generate. Important clues into the structure-toxicity relation of amyloids, the role performed by natural surfaces in oligomer growth and the molecular basis of oligomer-membrane interaction are also emerging.
Export Options
About this article
Cite this article as:
Stefani Massimo, Structural Polymorphism of Amyloid Oligomers and Fibrils Underlies Different Fibrillization Pathways: Immunogenicity and Cytotoxicity, Current Protein & Peptide Science 2010; 11 (5) . https://dx.doi.org/10.2174/138920310791330631
DOI https://dx.doi.org/10.2174/138920310791330631 |
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
-
Glutamine, Glucose and other Fuels for Cancer
Current Pharmaceutical Design High Glucose Enhances Neurotoxicity and Inflammatory Cytokine Secretion by Stimulated Human Astrocytes
Current Alzheimer Research Amplicons as Vaccine Vectors
Current Gene Therapy Muscarinic Acetylcholine Receptors: New Potential Therapeutic Targets in Antinociception and in Cancer Therapy
Recent Patents on CNS Drug Discovery (Discontinued) A Proteomic Analysis of Mitochondrial Complex III Inhibition in SH-SY5Y Human Neuroblastoma Cell Line
Current Proteomics Exploring Mechanisms of MicroRNA Downregulation in Cancer
MicroRNA Endoplasmic Reticulum Protein Quality Control in Neurodegenerative Disease: The Good, the Bad and the Therapy
Current Medicinal Chemistry Cannabis sativa L. Constituents and Their Role in Neuroinflammation
Current Bioactive Compounds Modular Nanotransporters for Targeted Intracellular Delivery of Drugs: Folate Receptors as Potential Targets
Current Pharmaceutical Design Involvement of Uridine-Nucleotide-Stimulated P2Y Receptors in Neuronal Growth and Function
Central Nervous System Agents in Medicinal Chemistry Anticonvulsant and Antinociceptive Actions of Novel Adenosine Kinase Inhibitors
Current Topics in Medicinal Chemistry Incorporation of Anti-angiogenic Therapies in the Treatment of Epithelial Ovarian Cancer: Current Perspectives and Future Directions
Current Angiogenesis (Discontinued) Gap Junctions as Targets for Cancer Chemoprevention and Chemotherapy
Current Drug Targets Therapeutic Targeting of Malignant Glioma
Anti-Cancer Agents in Medicinal Chemistry Targeting Transcription Factor Binding to DNA by Competing with DNA Binders as an Approach for Controlling Gene Expression
Current Topics in Medicinal Chemistry Extracellular Targeting of Synthetic Therapeutic Nucleic Acid Formulations
Current Gene Therapy Natural Thiazoline-Based Cyclodepsipeptides from Marine Cyanobacteria: Chemistry, Bioefficiency and Clinical Aspects
Current Medicinal Chemistry Acute Hypersensitivity Reactions to Chemotherapy Agents: An Overview
Inflammation & Allergy - Drug Targets (Discontinued) The Wnt Pathway in Mood Disorders
Current Neuropharmacology T Cell Costimulatory and Inhibitory Receptors as Therapeutic Targets for Inducing Anti-Tumor Immunity
Current Cancer Drug Targets