Amyloid Fibrils and Prefibrillar Aggregates - Molecular and Biological Properties

Summing up almost a decade of biomedical research, this topical and eagerly awaited handbook is the first reference on the topic to incorporate recent breakthroughs in amyloid research.The first part covers the structural biology of amyloid fibrils and pre-fibrillar assemblies, including a description of current models for amyloid formation. The second part looks at the diagnosis and biomedical study of amyloid in humans and in animal models, while the final section discusses pharmacological approaches to manipulating amyloid and also looks at its physiological roles in lower and higher organisms. For Biochemists, Molecular Biologists, Neurobiologists, Neurophysiologists and those working in the Pharmaceutical Industry.

List of contents

PREFACETHE AMYLOID PHENOMENON AND ITS SIGNIFICANCE Introduction The Nature of the Amyloid State of Proteins The Structure and Properties of Amyloid Species The Kinetics and Mechanism of Amyloid Formation The Link between Amyloid Formation and Disease Strategies for Therapeutic InterventionLooking to the Future Summary AMYLOID STRUCTURES AT THE ATOMIC LEVEL: INSIGHTS FROM CRYSTALLOGRAPHY Atomic Structures of Segments of Amyloid-Forming Proteins Stability of Amyloid Fibers Which Proteins Enter the Amyloid State? Molecular Basis of Amyloid Polymorphism and Prion Strains Atomic Structures of Steric Zippers Suggest Models for Amyloid Fibers of Parent Proteins Atomic Structures of Steric Zippers Offer Approaches for Chemical Interventions against Amyloid Formation Summary WHAT DOES SOLID-STATE NMR TELL US ABOUT AMYLOID STRUCTURES? Introduction Principles of Solid-State NMR Spectroscopy and Experiments for Structural ConstraintsAmyloid Fibrils Investigated by Solid-State NMR SpectroscopySummaryFROM MOLECULAR TO SUPRAMOLECULAR AMYLOID STRUCTURES: CONTRIBUTIONS FROM FIBER DIFFRACTION AND ELECTRON MICROSCOPY IntroductionHistory Methodology Recent Advances in Amyloid Structure Determination Summary STRUCTURES OF AGGREGATING SPECIES BY SMALL-ANGLE X-RAY SCATTERING IntroductionTheoretical and Experimental Aspects Data Analysis and Modeling Methods Studying Protein Aggregation and Fibrillation Using SAXS General Strategies for Modeling SAXS Data from Protein ComplexesSummary and Final Remarks STRUCTURAL AND COMPOSITIONAL INFORMATION ABOUT PRE-AMYLOID OLIGOMERS General Introduction Biophysical Techniques to Study Amyloid Oligomers The Structure and Composition of Amyloid Oligomers Concluding Remarks THE OLIGOMER SPECIES: MECHANISTICS AND BIOCHEMISTRY Introduction The Structure - Toxicity Relation of Early Amyloids The Oligomer - Membrane Complex Biochemical Modifications Underlying Amyloid Toxicity Summary PATHWAYS OF AMYLOID FORMATION Introduction Nomenclature of the Various Conformational States Graphical Representations of the Mechanisms Leading to Amyloid Pathways of Amyloid Fibril FormationNucleation Growth versus Nucleated Conformational Conversion Summary SEQUENCE-BASED PREDICTION OF PROTEIN BEHAVIOR Introduction The Strategy of the Zyggregator Predictions Aggregation Under Other Conditions Prediction of the Cellular Toxicity of Protein Aggregates Relationship to Other Methods of Predicting Protein Aggregation Propensities Competition between Folding and Aggregation of Proteins Prediction of Protein Solubility from the Competition between Folding and Aggregation Sequence-Based Prediction of Protein Interactions with Molecular Chaperones Summary THE KINETICS AND MECHANISMS OF AMYLOID FORMATION Introduction Classical Theory of Nucleated Polymerization The Theory of Filamentous Growth with Secondary Pathways Self-Consistent Solutions for the Complete Reaction Time Course Summary FLUORESCENCE SPECTROSCOPY AS A TOOL TO CHARACTERIZE AMYLOID OLIGOMERS AND FIBRILS Introduction Fluorescence Spectroscopy for Studies of Amyloid Reactions In vitro Cysteine-Reactive Fluorescent Probes Amyloidotropic Probes for Amyloid Fibrils and Oligomeric States Luminescent Conjugated Poly and Oligothiophenes LCPs and LCOs Summary ANIMAL MODELS OF AMYLOID DISEASES Introduction Some Big Questions Regarding Amyloid Diseases and Some Answers from Animal Models Identifying the Toxic Species in the Systemic AmyloidosesIdentifying the Toxic Species in Alzheimer's Disease Infectious Protein MisfoldingConclusions THE ROLE OF AB IN ALZHEIMER'S DISEASE History of Amyloidosis Biochemistry of Aß Amyloid Fibrils The Soluble Oligomer Theory of AD Other Factors Involved in Amyloid Plaque Formation in AD Metal Ions in AD Other Potential Aß Interactions Other Neurodegenerative Diseases Conclusion EXPERIMENTAL APPROACHES TO INDUCING AMYLOID AGGREGATES The Need for Reproducible Fibrillation Assays Setting Up an Assay to Monitor Fibrillation Conditions That Promote Protein Aggregation Processing and Batch Differences Toward High-Throughput Assays Summary FIBRILLAR POLYMORPHISM Detection of Fibrillar Polymorphism The Structural Definition of Fibril Polymorphism The Two Classes of Fibril Polymorphism How Does Fibrillar Polymorphism Arise? The Interconversion of Fibril Polymorphs The Biological Implications of Fibril Polymorphism Summary INHIBITORS OF AMYLOID AND OLIGOMER FORMATION Introduction: Amyloidoses versus Neurodegenerative Diseases Summary DEVELOPMENT OF THERAPEUTIC STRATEGIES FOR THE TRANSTHYRETIN AMYLOIDOSES Introduction to Transthyretin Structure and Function Introduction to Amyloid Diseases in General Mechanism of Transthyretin Amyloidogenesis Kinetic Stabilization of the Transthyretin Tetramer through Small-Molecule Binding Assessment of Diflunisal for Treatment of Transthyretin Amyloidosis Tafamidis, the First Approved Drug for Treatment of a Transthyretin Amyloidosis Summary HORMONE AMYLOIDS IN SICKNESS AND IN HEALTH Introduction Constitutive vs. Regulated Secretory Pathways Secretory Granules Contain Aggregated Cargo Secretory Granule Aggregation by Functional Amyloid Formation Hormone Amyloids in Disease: Diabetes Insipidus Conclusions FUNCTIONAL AMYLOIDS IN BACTERIA Introduction Functional Amyloids are Common in Nature Identification and Characterization of Functional Amyloids Functional Bacterial Amyloids Play Many Roles Biogenesis and Regulation of Functional Bacterial Amyloids Structural Composition of Functional Amyloids Assembly Properties of Functional Amyloid In Vitro Diversity and Distribution of Functional Amyloid Genes Summary STRUCTURAL PROPERTIES AND APPLICATIONS OF SELF-ASSEMBLING PEPTIDES Introduction to Self-Assembling Peptides The Principles of Self-Assembling Peptides Self-Assembling Peptide Nanofibers Diverse Applications of Self-Assembling Peptide Nanofibers Scaffolds Summary HARNESSING THE SELF-ASSEMBLING PROPERTIES OF PROTEINS IN SPIDER SILK AND LUNG SURFACTANTIntroduction Amino Acid Sequences and Amyloid Formation Spider Silk and How the Spiders Make It Harnessing the Properties of Spider Silk and Its Constituent Proteins Biosynthesis of an a-Helix from One of the Most ß-Prone Sequences Known Anti-Amyloid Properties of the BRICHOS Domain Summary INDEX

About the author

Daniel Erik Otzen is Professor at the Interdisciplinary Nanoscience Centre of the Department of Molecular Biology at Aarhus University, Denmark. A graduate of Aarhus University, he obtained a Ph.D. in protein biophysics from the universities of Aarhus and Cambridge (UK). In 1995, he began work as a research chemist at Novo Nordisk, followed by post-doctoral work at Lund University (Sweden). In 2000, he joined the faculty of Aalborg University before taking up his current appointment at Aarhus in 2007. Professor Otzen has received several awards, including the Prize of the Alzheimer Research Foundation, the Carlsberg Biotechnology Prize and the Silver Medal of the Royal Danish Society. He has published more than 120 research articles and serves as an editor for the journals Biochimica Biophysica Acta and Biophysical Chemistry.

Summary

Summing up almost a decade of biomedical research, this topical and eagerly awaited handbook is the first reference on the topic to incorporate recent breakthroughs in amyloid research.

The first part covers the structural biology of amyloid fibrils and pre-fibrillar assemblies, including a description of current models for amyloid formation. The second part looks at the diagnosis and biomedical study of amyloid in humans and in animal models, while the final section discusses pharmacological approaches to manipulating amyloid and also looks at its physiological roles in lower and higher organisms. For Biochemists, Molecular Biologists, Neurobiologists, Neurophysiologists and those working in the Pharmaceutical Industry.

Product details

• Authors: Daniel Erik Otzen
• Assisted by: Danie Erik Otzen (Editor), Daniel Erik Otzen (Editor), Daniel E. Otzen (Editor), Daniel Erik Otzen (Editor)
• Publisher: Wiley-VCH
• Languages: English
• Product format: Hardback
• Released: 01.02.2013
• EAN: 9783527332007
• ISBN: 978-3-527-33200-7
• No. of pages: 448
• Dimensions: 177 mm x 249 mm x 30 mm
• Weight: 1214 g
• Illustrations: 30 SW-Abb., 82 Farbabb., 25 Tabellen
• Subjects: Natural sciences, medicine, IT, technology > Chemistry > Organic chemistry; Chemie, Medizin, Molekularbiologie, Proteine, Life Sciences, Biowissenschaften, molecular biology, chemistry, Amyloid, Protein Science, Medical Science, Strukturbiologie, Structural Biology, Fibrille