Protein Misfolding, Aggregation and Conformational Diseases (eBook)

Part A: Protein Aggregation and Conformational Diseases

Anthony Fink, Vladimir N. Uversky (Herausgeber)

eBook Download: PDF

2007 | 2006
XVIII, 419 Seiten
Springer US (Verlag)
978-0-387-25919-2 (ISBN)

Infos

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.

Inhalt

Contents 6
Contributors 18
Structural and Conformational Prerequisites of Amyloidogenesis 20
1. Abstract 20
2. Introduction 20
3. What Kind of Defects in the Soluble Folded State Bolster the Conversion to the Amyloidogenic Phase? 25
4. What Are the Conformational Prerequisites for Partially Folded Intermediates to Become the Amyloidogenic Species? 26
5. Concluding Remarks 33
6. Abbreviations 33
References 33
The Generic Nature of Protein Folding and Misfolding 40
1. Abstract 40
2. Introduction 40
3. The Universal Mechanism of Protein Folding 41
4. Protein Folding and Misfolding in the Cellular Environment 43
5. The Generic Nature of Amyloid Formation 45
6. Common Features of Protein Self-Assembly 49
7. Generic Aspects of Misfolding Diseases 51
8. Common Strategies for Therapeutic Intervention 53
9. Concluding Remarks 55
10. Abbreviations 55
Acknowledgments 55
References 56
Relative Importance of Hydrophobicity, Net Charge, and Secondary Structure Propensities in Protein Aggregation 61
1. Abstract 61
2. Introduction 61
3. Importance of Hydrophobicity in Protein Aggregation 62
4. Importance of Charge in Protein Aggregation 65
5. Importance of the Propensity to a Form Secondary Structure in Protein Aggregation 68
6. Mutations Modulate Aggregation as a Result of Their Effects on Simple Physicochemical Determinants 70
7. Amino Acid Sequences Have Evolved to Take into Account the Influence of Hydrophobicity, Charge, and b-Sheet Propensity in Protein Aggregation 71
8. Other Factors Involved in Protein Aggregation 72
9. Is Protein Aggregation Driven by Specifi c Sequences? 73
10. Future Perspectives 73
11. Abbreviations 74
References 74
Cytotoxic Intermediates in the Fibrillation Pathway: Ab Oligomers in Alzheimer’s Disease as a Case Study 78
1. Abstract 78
2. AD Is a Dementia Involving the Fibrillogenic Ab Peptide 78
3. Why the Fibril- Based Cascade Hypothesis Unraveled: A Singular Illustration with a Transgenic Mouse AD Model 80
4. If Not Fibrils, What? Discovery of Ab’s Hidden Toxins 80
5. Oligomers Have Profound Neurological Impact, Accounting for Reversibility of Memory Loss 81
6. How Oligomers Attack Neurons— A Molecular Mechanism for Why AD Is Specifi c for Memory Loss 82
7. Immediate Consequences of Oligomer Binding: Signal Transduction Targets 83
8. Cascading Consequences— Can Oligomer- Induced Synapse Dysfunction Lead to Synapse Destruction and Neuron Death? 84
9. In Vivo Experimental Support for Synaptotoxic Oligomers: Data from Mouse Models of Early AD 84
10. Clinical Validation— Oligomers in Human Brain, Elevated up to 70- Fold in AD 85
11. New “Oligomer- Driven” Amyloid Hypothesis 86
12. Mechanisms of Ab Oligomerization and Fibrillogenesis 86
13. Pathogenic Ab Oligomers— First of Many? All Proteins Likely Have the Capacity to Oligomerize 88
14. Therapeutics and Diagnostics— New Strategies 90
15. Abbreviations 92
Acknowledgments 92
Potential Conflicts 92
References 92
Glycosaminoglycans, Proteoglycans, and Conformational Disorders 99
1. Abstract 99
2. Biochemical Properties of Proteoglycans and Glycosaminoglycans 99
3. Neurodegenerative Diseases Are Protein Conformational Disorders 101
4. Proteoglycans Contribute to Protein Misfolding in Conformational Protein Disorders Outside the Nervous System 108
5. Conclusions 110
6. Abbreviations 111
References 111
Apolipoproteins in Different Amyloidoses 117
1. Abstract 117
2. Introduction 117
3. Molecular Characteristic of Apolipoproteins Involved in Amyloidoses 119
4. Role of Apolipoproteins in Pathological Mechanism of AD Amyloidosis 120
5. Apolipoproteins in Prion Diseases 125
6. Apolipoproteins in Other Amyloidoses 126
7. Apolipoproteins as a Substrate of Amyloid Fibrils 127
8. Apolipoproteins as a Therapeutic Target in Amyloidoses 127
9. Abbreviations 128
References 129
Oxidative Stress and Protein Deposition Diseases 139
1. Abstract 139
2. Introduction to Oxidative and Nitrative Stresses 139
3. Oxidative and Nitrative Stresses in Neurodegenerative Diseases with Protein Deposits 141
4. Abbreviations 146
References 146
Chaperone and Conformational Disorders 150
Chaperone Suppression of Aggregated Protein Toxicity 151
1. Abstract 151
2. Protein Folding and Misfolding 151
3. Cellular Quality Control 152
4. Mutations in Molecular Chaperones Responsible for Human Disease 154
5. Protein Misfolding Diseases 154
6. Protein Aggregates: A Common Denominator of Neurodegenerative Disease 156
7. Molecular Chaperones: Key Regulators of Protein Aggregation and Toxicity 157
8. Chaperones as a Potential Drug Target 169
9. Abbreviations 170
References 170
Mechanisms of Active Solubilization of Stable Protein Aggregates by Molecular Chaperones 179
1. Abstract 179
2. Choosing Between Native Folding and Misfolding 179
3. Many Molecular Chaperones Can Prevent Protein Aggregation 180
4. Some ATPase Chaperones Can Solubilize and Reactivate Stable Protein Aggregates 181
5. Prevention of Aggregation Is Not Required for Chaperone- Dependent Protein Refolding 181
6. ATPase Chaperones Can Unfold Misfolded Proteins 181
7. Ring- Shaped Chaperone Oligomers Can Use Power Strokes to Actively Unfold Aggregates 182
8. Individual Chaperone Monomers Can Use Random Motions to Actively Unfold Aggregates 183
9. Conclusion: The Successive Lines of Defense Against Protein Aggregation and Diseases 184
10. Abbreviation 185
Acknowledgments 185
References 185
The Aggresome: Proteasomes, Inclusion Bodies, and Protein Aggregation 213
1. Abstract 213
2. Introduction 213
3. Characteristics of Aggresomes 214
4. Examples of Aggresomes in Human Health and Disease 222
5. Mechanisms of Aggresome Formation 237
6. Future Directions 245
7. Abbreviations 246
References 246
Protein Aggregation, Ion Channel Formation, and Membrane Damage 261
1. Abstract 261
2. Introduction 261
3. Alzheimer’s Disease ( Ab) 263
4. Prion ( PrP) Channels 265
5. Type II Diabetes Mellitus and Islet Amyloid Polypeptide ( IAPP, Amylin) 266
6. a-Synuclein and Parkinson’s Disease 267
7. Polyglutamine and Triplet Repeat Diseases 267
8. Mechanisms of Membrane- Mediated Damage 268
9. Abbreviations 271
References 271
Visualization of Protein Deposits 275
Congo Red Staining of Amyloid: Improvements and Practical Guide for a More Precise Diagnosis of Amyloid and the Different Amyloidoses 276
1. Abstract 276
2. Amyloidosis 276
3. Identification of Amyloid Using Dyes 278
4. The Chemical Structure of CR and Some Properties 283
5. Concerning the Specificity of CR 286
6. Concerning the Practical Use of CR 287
7. Chemical Identification of Amyloidosis 292
8. Advice for the Immunohistochemical Classifi cation of Amyloids 297
9. From Bench to Bedside: An Algorithm for a Reliable Diagnosis 299
10. Quantification of Amyloid 302
11. Novel Techniqes in Amyloid Research 303
12. Abbreviations 304
Acknowledgments 304
References 304
Immunohistological Study of Experimental Murine AA Amyloidosis 314
1. Abstract 314
2. Introduction 314
3. Amyloid Induction 315
4. Detection of Components of Amyloid Fibrils and Macrophages 316
5. Induction of Amyloid Deposition in the Marginal Zone 317
6. Time- kinetic Detection of Amyloid Components and Macrophages by Double Immunofl uorescence Method 317
7. Formation of Amyloid Fibrils 318
8. Resorption of Amyloid Fibrils 319
9. Abbreviations 319
References 319
Visualization of Protein Deposits 321
Reporters of Amyloid Structure 322
1. Abstract 322
2. Common Elements of Amyloid Fibrils 322
3. Probes in Which Amyloid Fibrils Induce Changes 323
4. Tight Binding Probes for Amyloid Imaging 325
5. The Phenomenon of Cognate Peptide Recognition 327
6. Conformation- Dependent Antibodies 328
7. Abbreviations 331
Acknowledgments 331
References 331
Three- Dimensional Structural Analysis of Amyloid Fibrils by Electron Microscopy 338
1. Abstract 338
2. Introduction: Structural Studies 338
3. Amyloid Fibril Structure and the Cross-b Fold 338
4. EM Methods for Amyloid 340
5. Results of EM Studies 343
6. Prospects for Fibril Structure Determination 346
7. Abbreviations 346
References 346
Atomic Force Microscopy 349
1. Abstract 349
2. Introduction 349
3. AFM 350
4. Studies of Ab Peptide Aggregation and Morphology 351
5. Studies of a-Syn Aggregation and Morphology 358
6. Studies of Other Amyloid- Forming Peptides 364
7. Conclusions 365
8. Abbreviations 365
References 365
Direct Observation of Amyloid Fibril Growth Monitored by Total Internal Refl ection Fluorescence Microscopy 369
1. Abstract 369
2. Introduction 369
3. Experimental Procedures 370
4. Results and Discussion 371
5. Conclusion 375
6. Abbreviations 376
Acknowledgments 376
References 376
Animal and Cell Models of Human Neurodegenerative Disorders 378
Drosophila and C. elegans Models of Human Age-Associated Neurodegenerative Diseases 379
1. Abstract 379
2. Introduction 379
3. Modeling Human Polyglutamine Diseases 380
4. Modeling Noncoding Trinucleotide Repeat Diseases 386
5. Modeling PD 387
6. Modeling Alzheimer’s and Related Diseases 391
7. Future Directions 394
8. Abbreviations 395
Acknowledgments 396
References 396
Genetically Engineered Mouse Models of Neurodegenerative Disorders 402
1. Abstract 402
2. Introduction 402
3. Alzheimer’s Disease and Cerebrovascular Amyloidosis 405
4. Fronto- temporal Dementias and Tauopathies 412
5. Lewy Body Dementia and PD 415
6. Amyotrophic Lateral Sclerosis 421
7. Neurodegenerative Disorders with Trinucleotide Repeats 422
8. Conclusions 424
9. Abbreviations 424
Acknowledgments 426
References 426
Index 440

Produkt-Details

• Erscheint lt. Verlag: 24.11.2007
• Reihe/Serie: Protein Reviews
• Zusatzinfo: XVIII, 420 p. 104 illus., 46 illus. in color.
• Verlagsort: New York
• Sprache: englisch
• Themenwelt: Studium ► 1. Studienabschnitt (Vorklinik) ► Biochemie / Molekularbiologie
• Themenwelt: Studium ► Querschnittsbereiche ► Infektiologie / Immunologie
• Themenwelt: Naturwissenschaften ► Biologie
• Themenwelt: Technik
• Schlagworte: Aggregation • Conformational • Disease • electron microscopy • Misfolding • Molecular Biology • Protein • Proteoglycans • Uversky
• ISBN-10: 0-387-25919-8 / 0387259198
• ISBN-13: 978-0-387-25919-2 / 9780387259192