Uversky / Fink Protein Misfolding, Aggregation and Conformational Diseases

Part A: Protein Aggregation and Conformational Diseases
1. Auflage 2007
ISBN: 978-0-387-25919-2
Verlag: Springer US
Format: PDF
Kopierschutz: 1 - PDF Watermark

E-Book, Englisch, Band 4, 419 Seiten

Reihe: Protein Reviews

Research indicates that most neurodegenerative diseases, systemic amyloidoses and many others, arise from the misfolding and aggregation of an underlying protein. This is the first book to discuss significant achievements in protein structure-function relationships in biochemistry, molecular biology and molecular medicine. The authors summarize recent progress in the understanding of the relationships between protein misfolding, aggregation and development of protein deposition disorders.

Autoren/Hrsg.

Uversky, Vladimir N.

Fink, Anthony

Inhaltsverzeichnis

1;Contents;6
2;Contributors;18
3;Structural and Conformational Prerequisites of Amyloidogenesis;20
3.1;1. Abstract;20
3.2;2. Introduction;20
3.3;3. What Kind of Defects in the Soluble Folded State Bolster the Conversion to the Amyloidogenic Phase?;25
3.4;4. What Are the Conformational Prerequisites for Partially Folded Intermediates to Become the Amyloidogenic Species?;26
3.5;5. Concluding Remarks;33
3.6;6. Abbreviations;33
3.7;References;33
4;The Generic Nature of Protein Folding and Misfolding;40
4.1;1. Abstract;40
4.2;2. Introduction;40
4.3;3. The Universal Mechanism of Protein Folding;41
4.4;4. Protein Folding and Misfolding in the Cellular Environment;43
4.5;5. The Generic Nature of Amyloid Formation;45
4.6;6. Common Features of Protein Self-Assembly;49
4.7;7. Generic Aspects of Misfolding Diseases;51
4.8;8. Common Strategies for Therapeutic Intervention;53
4.9;9. Concluding Remarks;55
4.10;10. Abbreviations;55
4.11;Acknowledgments;55
4.12;References;56
5;Relative Importance of Hydrophobicity, Net Charge, and Secondary Structure Propensities in Protein Aggregation;61
5.1;1. Abstract;61
5.2;2. Introduction;61
5.3;3. Importance of Hydrophobicity in Protein Aggregation;62
5.4;4. Importance of Charge in Protein Aggregation;65
5.5;5. Importance of the Propensity to a Form Secondary Structure in Protein Aggregation;68
5.6;6. Mutations Modulate Aggregation as a Result of Their Effects on Simple Physicochemical Determinants;70
5.7;7. Amino Acid Sequences Have Evolved to Take into Account the Influence of Hydrophobicity, Charge, and b-Sheet Propensity in Protein Aggregation;71
5.8;8. Other Factors Involved in Protein Aggregation;72
5.9;9. Is Protein Aggregation Driven by Specifi c Sequences?;73
5.10;10. Future Perspectives;73
5.11;11. Abbreviations;74
5.12;References;74
6;Cytotoxic Intermediates in the Fibrillation Pathway: Ab Oligomers in Alzheimer’s Disease as a Case Study;78
6.1;1. Abstract;78
6.2;2. AD Is a Dementia Involving the Fibrillogenic Ab Peptide;78
6.3;3. Why the Fibril- Based Cascade Hypothesis Unraveled: A Singular Illustration with a Transgenic Mouse AD Model;80
6.4;4. If Not Fibrils, What? Discovery of Ab’s Hidden Toxins;80
6.5;5. Oligomers Have Profound Neurological Impact, Accounting for Reversibility of Memory Loss;81
6.6;6. How Oligomers Attack Neurons— A Molecular Mechanism for Why AD Is Specifi c for Memory Loss;82
6.7;7. Immediate Consequences of Oligomer Binding: Signal Transduction Targets;83
6.8;8. Cascading Consequences— Can Oligomer- Induced Synapse Dysfunction Lead to Synapse Destruction and Neuron Death?;84
6.9;9. In Vivo Experimental Support for Synaptotoxic Oligomers: Data from Mouse Models of Early AD;84
6.10;10. Clinical Validation— Oligomers in Human Brain, Elevated up to 70- Fold in AD;85
6.11;11. New “Oligomer- Driven” Amyloid Hypothesis;86
6.12;12. Mechanisms of Ab Oligomerization and Fibrillogenesis;86
6.13;13. Pathogenic Ab Oligomers— First of Many? All Proteins Likely Have the Capacity to Oligomerize;88
6.14;14. Therapeutics and Diagnostics— New Strategies;90
6.15;15. Abbreviations;92
6.16;Acknowledgments;92
6.17;Potential Conflicts;92
6.18;References;92
7;Glycosaminoglycans, Proteoglycans, and Conformational Disorders;99
7.1;1. Abstract;99
7.2;2. Biochemical Properties of Proteoglycans and Glycosaminoglycans;99
7.3;3. Neurodegenerative Diseases Are Protein Conformational Disorders;101
7.4;4. Proteoglycans Contribute to Protein Misfolding in Conformational Protein Disorders Outside the Nervous System;108
7.5;5. Conclusions;110
7.6;6. Abbreviations;111
7.7;References;111
8;Apolipoproteins in Different Amyloidoses;117
8.1;1. Abstract;117
8.2;2. Introduction;117
8.3;3. Molecular Characteristic of Apolipoproteins Involved in Amyloidoses;119
8.4;4. Role of Apolipoproteins in Pathological Mechanism of AD Amyloidosis;120
8.5;5. Apolipoproteins in Prion Diseases;125
8.6;6. Apolipoproteins in Other Amyloidoses;126
8.7;7. Apolipoproteins as a Substrate of Amyloid Fibrils;127
8.8;8. Apolipoproteins as a Therapeutic Target in Amyloidoses;127
8.9;9. Abbreviations;128
8.10;References;129
9;Oxidative Stress and Protein Deposition Diseases;139
9.1;1. Abstract;139
9.2;2. Introduction to Oxidative and Nitrative Stresses;139
9.3;3. Oxidative and Nitrative Stresses in Neurodegenerative Diseases with Protein Deposits;141
9.4;4. Abbreviations;146
9.5;References;146
10;Chaperone and Conformational Disorders;150
10.1;Chaperone Suppression of Aggregated Protein Toxicity;151
10.1.1;1. Abstract;151
10.1.2;2. Protein Folding and Misfolding;151
10.1.3;3. Cellular Quality Control;152
10.1.4;4. Mutations in Molecular Chaperones Responsible for Human Disease;154
10.1.5;5. Protein Misfolding Diseases;154
10.1.6;6. Protein Aggregates: A Common Denominator of Neurodegenerative Disease;156
10.1.7;7. Molecular Chaperones: Key Regulators of Protein Aggregation and Toxicity;157
10.1.8;8. Chaperones as a Potential Drug Target;169
10.1.9;9. Abbreviations;170
10.1.10;References;170
10.2;Mechanisms of Active Solubilization of Stable Protein Aggregates by Molecular Chaperones;179
10.2.1;1. Abstract;179
10.2.2;2. Choosing Between Native Folding and Misfolding;179
10.2.3;3. Many Molecular Chaperones Can Prevent Protein Aggregation;180
10.2.4;4. Some ATPase Chaperones Can Solubilize and Reactivate Stable Protein Aggregates;181
10.2.5;5. Prevention of Aggregation Is Not Required for Chaperone- Dependent Protein Refolding;181
10.2.6;6. ATPase Chaperones Can Unfold Misfolded Proteins;181
10.2.7;7. Ring- Shaped Chaperone Oligomers Can Use Power Strokes to Actively Unfold Aggregates;182
10.2.8;8. Individual Chaperone Monomers Can Use Random Motions to Actively Unfold Aggregates;183
10.2.9;9. Conclusion: The Successive Lines of Defense Against Protein Aggregation and Diseases;184
10.2.10;10. Abbreviation;185
10.2.11;Acknowledgments;185
10.2.12;References;185
11;The Aggresome: Proteasomes, Inclusion Bodies, and Protein Aggregation;213
11.1;1. Abstract;213
11.2;2. Introduction;213
11.3;3. Characteristics of Aggresomes;214
11.4;4. Examples of Aggresomes in Human Health and Disease;222
11.5;5. Mechanisms of Aggresome Formation;237
11.6;6. Future Directions;245
11.7;7. Abbreviations;246
11.8;References;246
12;Protein Aggregation, Ion Channel Formation, and Membrane Damage;261
12.1;1. Abstract;261
12.2;2. Introduction;261
12.3;3. Alzheimer’s Disease ( Ab);263
12.4;4. Prion ( PrP) Channels;265
12.5;5. Type II Diabetes Mellitus and Islet Amyloid Polypeptide ( IAPP, Amylin);266
12.6;6. a-Synuclein and Parkinson’s Disease;267
12.7;7. Polyglutamine and Triplet Repeat Diseases;267
12.8;8. Mechanisms of Membrane- Mediated Damage;268
12.9;9. Abbreviations;271
12.10;References;271
13;Visualization of Protein Deposits;275
13.1;Congo Red Staining of Amyloid: Improvements and Practical Guide for a More Precise Diagnosis of Amyloid and the Different Amyloidoses;276
13.1.1;1. Abstract;276
13.1.2;2. Amyloidosis;276
13.1.3;3. Identification of Amyloid Using Dyes;278
13.1.4;4. The Chemical Structure of CR and Some Properties;283
13.1.5;5. Concerning the Specificity of CR;286
13.1.6;6. Concerning the Practical Use of CR;287
13.1.7;7. Chemical Identification of Amyloidosis;292
13.1.8;8. Advice for the Immunohistochemical Classifi cation of Amyloids;297
13.1.9;9. From Bench to Bedside: An Algorithm for a Reliable Diagnosis;299
13.1.10;10. Quantification of Amyloid;302
13.1.11;11. Novel Techniqes in Amyloid Research;303
13.1.12;12. Abbreviations;304
13.1.13;Acknowledgments;304
13.1.14;References;304
13.2;Immunohistological Study of Experimental Murine AA Amyloidosis;314
13.2.1;1. Abstract;314
13.2.2;2. Introduction;314
13.2.3;3. Amyloid Induction;315
13.2.4;4. Detection of Components of Amyloid Fibrils and Macrophages;316
13.2.5;5. Induction of Amyloid Deposition in the Marginal Zone;317
13.2.6;6. Time- kinetic Detection of Amyloid Components and Macrophages by Double Immunofl uorescence Method;317
13.2.7;7. Formation of Amyloid Fibrils;318
13.2.8;8. Resorption of Amyloid Fibrils;319
13.2.9;9. Abbreviations;319
13.2.10;References;319
14;Visualization of Protein Deposits;321
14.1;Reporters of Amyloid Structure;322
14.1.1;1. Abstract;322
14.1.2;2. Common Elements of Amyloid Fibrils;322
14.1.3;3. Probes in Which Amyloid Fibrils Induce Changes;323
14.1.4;4. Tight Binding Probes for Amyloid Imaging;325
14.1.5;5. The Phenomenon of Cognate Peptide Recognition;327
14.1.6;6. Conformation- Dependent Antibodies;328
14.1.7;7. Abbreviations;331
14.1.8;Acknowledgments;331
14.1.9;References;331
14.2;Three- Dimensional Structural Analysis of Amyloid Fibrils by Electron Microscopy;338
14.2.1;1. Abstract;338
14.2.2;2. Introduction: Structural Studies;338
14.2.3;3. Amyloid Fibril Structure and the Cross-b Fold;338
14.2.4;4. EM Methods for Amyloid;340
14.2.5;5. Results of EM Studies;343
14.2.6;6. Prospects for Fibril Structure Determination;346
14.2.7;7. Abbreviations;346
14.2.8;References;346
14.3;Atomic Force Microscopy;349
14.3.1;1. Abstract;349
14.3.2;2. Introduction;349
14.3.3;3. AFM;350
14.3.4;4. Studies of Ab Peptide Aggregation and Morphology;351
14.3.5;5. Studies of a-Syn Aggregation and Morphology;358
14.3.6;6. Studies of Other Amyloid- Forming Peptides;364
14.3.7;7. Conclusions;365
14.3.8;8. Abbreviations;365
14.3.9;References;365
14.4;Direct Observation of Amyloid Fibril Growth Monitored by Total Internal Refl ection Fluorescence Microscopy;369
14.4.1;1. Abstract;369
14.4.2;2. Introduction;369
14.4.3;3. Experimental Procedures;370
14.4.4;4. Results and Discussion;371
14.4.5;5. Conclusion;375
14.4.6;6. Abbreviations;376
14.4.7;Acknowledgments;376
14.4.8;References;376
15;Animal and Cell Models of Human Neurodegenerative Disorders;378
15.1;Drosophila and C. elegans Models of Human Age-Associated Neurodegenerative Diseases;379
15.1.1;1. Abstract;379
15.1.2;2. Introduction;379
15.1.3;3. Modeling Human Polyglutamine Diseases;380
15.1.4;4. Modeling Noncoding Trinucleotide Repeat Diseases;386
15.1.5;5. Modeling PD;387
15.1.6;6. Modeling Alzheimer’s and Related Diseases;391
15.1.7;7. Future Directions;394
15.1.8;8. Abbreviations;395
15.1.9;Acknowledgments;396
15.1.10;References;396
15.2;Genetically Engineered Mouse Models of Neurodegenerative Disorders;402
15.2.1;1. Abstract;402
15.2.2;2. Introduction;402
15.2.3;3. Alzheimer’s Disease and Cerebrovascular Amyloidosis;405
15.2.4;4. Fronto- temporal Dementias and Tauopathies;412
15.2.5;5. Lewy Body Dementia and PD;415
15.2.6;6. Amyotrophic Lateral Sclerosis;421
15.2.7;7. Neurodegenerative Disorders with Trinucleotide Repeats;422
15.2.8;8. Conclusions;424
15.2.9;9. Abbreviations;424
15.2.10;Acknowledgments;426
15.2.11;References;426
16;Index;440