| Description |
1 online resource (xxviii, 481 pages) : illustrations |
| Contents |
Amyloid Fibrils and Prefibrillar Aggregates -- Contents -- Preface -- List of Contributors -- 1 The Amyloid Phenomenon and Its Significance -- 1.1 Introduction -- 1.2 The Nature of the Amyloid State of Proteins -- 1.3 The Structure and Properties of Amyloid Species -- 1.4 The Kinetics and Mechanism of Amyloid Formation -- 1.5 The Link between Amyloid Formation and Disease -- 1.6 Strategies for Therapeutic Intervention -- 1.7 Looking to the Future -- 1.8 Summary -- Acknowledgments -- References -- 2 Amyloid Structures at the Atomic Level: Insights from Crystallography -- 2.1 Atomic Structures of Segments of Amyloid-Forming Proteins -- 2.1.1 Protein Segments That Form Amyloid-Related Crystals -- 2.1.2 Atomic Structures of Fiber-Like Microcrystals -- 2.2 Stability of Amyloid Fibers -- 2.3 Which Proteins Enter the Amyloid State? -- 2.4 Molecular Basis of Amyloid Polymorphism and Prion Strains -- 2.5 Atomic Structures of Steric Zippers Suggest Models for Amyloid Fibers of Parent Proteins -- 2.6 Atomic Structures of Steric Zippers Offer Approaches for Chemical Interventions against Amyloid Formation -- 2.7 Summary -- Acknowledgments -- References -- 3 What Does Solid-State NMR Tell Us about Amyloid Structures? -- 3.1 Introduction -- 3.2 Principles of Solid-State NMR Spectroscopy and Experiments for Structural Constraints -- 3.2.1 Isotope Labeling, Magic Angle Spinning, Dipolar Coupling, and Resonance Assignment -- 3.2.2 De.ning the Amyloid Core by Magnetization Transfer from Water -- 3.2.3 Determining the Fibril Registry -- 3.2.4 Seeded versus Unseeded Fibrils -- 3.3 Amyloid Fibrils Investigated by Solid-State NMR Spectroscopy -- 3.3.1 AÝ peptides of Different Length -- 3.3.2 Islet Amyloid Polypeptide (IAPP/Amylin): Parallel and Antiparallel Steric Zippers -- 3.3.3 Ü-Synuclein: Polymorphism with Flexible Terminal Regions |
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3.3.4 PrP: Rearrangements to Maintain a Fibrillar Core Region -- 3.3.5 Yeast Prions with Glutamine/Asparagine-Rich Prion Domains: Sup35p, Ure2p, and Rnq1p -- 3.3.6 Functional Amyloid: the Yeast Prion HET-s -- 3.4 Summary -- References -- 4 From Molecular to Supramolecular Amyloid Structures: Contributions from Fiber Diffraction and Electron Microscopy -- 4.1 Introduction -- 4.2 History -- 4.2.1 The Historical Use of X-ray Fiber Diffraction -- 4.2.2 The Historical Use of Transmission Electron Microscopy -- 4.3 Methodology -- 4.3.1 X-Ray Fiber Diffraction -- 4.3.2 Transmission Electron Microscopy -- 4.4 Recent Advances in Amyloid Structure Determination -- 4.4.1 X-ray Fiber Diffraction -- 4.4.2 Transmission Electron Microscopy -- 4.5 Summary -- Acknowledgments -- References -- 5 Structures of Aggregating Species by Small-Angle X-Ray Scattering -- 5.1 Introduction -- 5.2 Theoretical and Experimental Aspects -- 5.3 Data Analysis and Modeling Methods -- 5.4 Studying Protein Aggregation and Fibrillation Using SAXS -- 5.4.1 Some General Considerations -- 5.4.2 SAXS Studies of Insulin, Glucagon, and Ü-Synuclein -- 5.4.3 SDS-Induced Aggregation of Ü-Synuclein -- 5.4.4 Multi-Component Fitting and Analysis of SAXS Data -- 5.5 General Strategies for Modeling SAXS Data from Protein Complexes -- 5.6 Summary and Final Remarks -- Acknowledgments -- References -- 6 Structural and Compositional Information about Pre-Amyloid Oligomers -- 6.1 General Introduction -- 6.2 Biophysical Techniques to Study Amyloid Oligomers -- 6.2.1 Fluorescence Spectroscopy -- 6.2.1.1 Ensemble Spectroscopy -- 6.2.1.2 Single-Molecule Spectroscopy -- 6.2.2 Atomic Force Microscopy -- 6.2.3 Absorbance and Circular Dichroism Spectroscopy -- 6.2.4 Small-Angle X-Ray Scattering -- 6.2.5 Mass Spectrometry -- 6.3 The Structure and Composition of Amyloid Oligomers -- 6.3.1 Ü-Synuclein Oligomers |
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6.3.1.1 Morphology -- 6.3.1.2 Oligomer Structure -- 6.3.1.3 Oligomer Composition -- 6.3.2 AÝ Peptide Oligomers -- 6.3.2.1 Morphology -- 6.3.2.2 Composition -- 6.4 Concluding Remarks -- Acknowledgments -- References -- 7 The Oligomer Species: Mechanistics and Biochemistry -- 7.1 Introduction -- 7.2 The Structure-Toxicity Relation of Early Amyloids -- 7.2.1 Antibodies Define Different Structural Classes of Oligomers and Fibrils -- 7.2.2 Proteins May Form Different Kinds of Oligomers with Different Structural and Biological Activities -- 7.3 The Oligomer-Membrane Complex -- 7.3.1 The Effect of Surfaces on Protein Misfolding and Aggregation -- 7.3.2 The Membrane Composition Affects Binding and Aggregation Processes -- 7.3.3 Complex Roles of Cholesterol and Gangliosides in Oligomer Cytotoxicity -- 7.4 Biochemical Modifications Underlying Amyloid Toxicity -- 7.4.1 A New View of the Amyloid Cascade Hypothesis -- 7.4.2 Amyloid Pores: a Mechanism for Cytotoxicity? -- 7.4.3 Other Mechanisms for Oligomer Cytotoxicity -- 7.4.3.1 Oxidative Stress and Amyloid Aggregates -- 7.4.3.2 Lipid Modification and Ca2+ Entry -- 7.4.3.3 The Complexity of Amyloid and Oligomer Polymorphism -- 7.5 Summary -- References -- 8 Pathways of Amyloid Formation -- 8.1 Introduction -- 8.2 Nomenclature of the Various Conformational States -- 8.3 Graphical Representations of the Mechanisms Leading to Amyloid -- 8.3.1 Time Course of Amyloid Content -- 8.3.2 Energy Landscapes of Amyloid Fibril Formation -- 8.3.3 Reaction Equilibria Involved in Amyloid Fibril Formation -- 8.4 Pathways of Amyloid Fibril Formation -- 8.5 Nucleation Growth versus Nucleated Conformational Conversion -- 8.6 Summary -- References -- 9 Sequence-Based Prediction of Protein Behavior -- 9.1 Introduction -- 9.2 The Strategy of the Zyggregator Predictions |
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9.2.1 Prediction of the Effects of Amino Acid Substitutions on Protein Aggregation Rates -- 9.2.2 Prediction of the Overall Aggregation Rates of Peptides and Proteins -- 9.2.3 Prediction of Aggregation-Prone Regions in Amino Acid Sequences -- 9.3 Aggregation Under Other Conditions -- 9.3.1 Prediction of Protein Aggregation-Prone Regions in the Presence of Denaturants -- 9.3.2 Prediction of Aggregation-Prone Regions in Native States of Proteins -- 9.4 Prediction of the Cellular Toxicity of Protein Aggregates -- 9.5 Relationship to Other Methods of Predicting Protein Aggregation Propensities -- 9.6 Competition between Folding and Aggregation of Proteins -- 9.7 Prediction of Protein Solubility from the Competition between Folding and Aggregation -- 9.7.1 Sequence-Based Prediction of Protein Solubility -- 9.7.2 Prediction of the Solubility of Proteins Based on Their Cellular Abundance -- 9.8 Sequence-Based Prediction of Protein Interactions with Molecular Chaperones -- 9.9 Summary -- References -- 10 The Kinetics and Mechanisms of Amyloid Formation -- 10.1 Introduction -- 10.2 Classical Theory of Nucleated Polymerization -- 10.2.1 From Microscopic Processes to a Master Equation -- 10.2.2 Kinetic Equations for Experimental Observables -- 10.2.3 Characteristics of Oosawa-Type Growth -- 10.2.3.1 Nucleation and Growth Occur Simultaneously -- 10.2.3.2 The Early Stages of the Reaction Time Course Are Described by Polynomial Growth -- 10.2.3.3 The Late Stages of the Reaction Time Course are Described by Simple First-Order Kinetics -- 10.2.3.4 The Integrated Rate Laws Exhibit Scaling Behavior -- 10.2.4 Global Analysis of Experimental Data Using the Oosawa Theory -- 10.3 The Theory of Filamentous Growth with Secondary Pathways -- 10.3.1 Extending the Oosawa Framework to Include Fragmentation and Secondary Nucleation -- 10.3.2 Early Time Perturbative Solutions |
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10.3.3 Characteristics of Exponential-Type Growth -- 10.3.3.1 The Early Stages of the Reaction Time Course Are Exponential -- 10.3.3.2 The Solution Exhibits Scaling Behavior -- 10.3.4 Global Analysis of Experimental Data Using Linearized Solutions -- 10.4 Self-Consistent Solutions for the Complete Reaction Time Course -- 10.4.1 The Key Phenomenological Parameters Depend on Combinations of the Microscopic Rate Constants -- 10.4.2 Reaction Time Course with Depleted Monomer Concentration -- 10.4.3 Global Analysis of Amyloid Reaction Kinetics Using Self-Consistent Solutions -- 10.5 Summary -- References -- 11 Fluorescence Spectroscopy as a Tool to Characterize Amyloid Oligomers and Fibrils -- 11.1 Introduction -- 11.2 Fluorescence Spectroscopy for Studies of Amyloid Reactions In vitro -- 11.2.1 Fluorescence Output Formats -- 11.2.2 Fluorescence Anisotropy -- 11.2.3 Single Molecule Detection -- 11.2.4 Conformational Probes -- 11.3 Cysteine-Reactive Fluorescent Probes -- 11.3.1 Environmentally Sensitive Probes -- Spectrochromic Stokes Shift Assay -- 11.3.2 Fluorescence Anisotropy Probes for Amyloid Oligomerization -- 11.3.3 Pyrene Excimer Formation Probes for amyloid Oligomer and Fibril Topology -- 11.3.4 Bifunctional Cysteine Reagents as Probes for Amyloid Oligomers and Fibrils -- 11.4 Amyloidotropic Probes for Amyloid Fibrils and Oligomeric States -- 11.4.1 Are There Selective Probes for Prefibrillar Oligomeric States? -- 11.4.2 Fluorescence Anisotropy of Small Molecule Probes for Capturing the Intermediate Oligomeric State -- 11.4.3 In vivo Fluorescent Probes for Amyloid Fibrils -- 11.5 Luminescent Conjugated Poly and Oligothiophenes LCPs and LCOs -- 11.5.1 Optical Properties of Chemically Defined LCOs -- 11.5.2 Bridging the Imaging and Spectroscopy Gap -- Microspectroscopy of In vivo Formed Amyloids |
| Summary |
Summing up almost a decade of biomedical research, this topical handbook is a reference on the topic which incorporates recent breakthroughs in amyloid research. The first part covers the structural biology of amyloid fibrils and pre-fibrillar assemblies. 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 |
| Bibliography |
Includes bibliographical references and index |
| Notes |
English |
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Print version record |
| Subject |
Amyloid.
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Amyloid -- chemistry
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Amyloid -- pharmacokinetics
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Amyloid
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SCIENCE -- Life Sciences -- Biochemistry.
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Amyloid
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Bioquímica.
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| Form |
Electronic book
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| Author |
Otzen, Daniel Erik, 1969-
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| ISBN |
9783527654215 |
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3527654216 |
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9781299633773 |
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1299633773 |
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3527654208 |
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9783527654208 |
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3527654186 |
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9783527654185 |
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