9780387259185

Protein Misfolding, Aggregation and Conformational Diseases

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  • ISBN13:

    9780387259185

  • ISBN10:

    038725918X

  • Edition: 1st
  • Format: Hardcover
  • Copyright: 2006-06-06
  • Publisher: Springer Verlag
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Supplemental Materials

What is included with this book?

Summary

This volume fills the gap in protein review/protocal literature while summarizing recent achievements in the understanding of the relationships between protein misfoldings, aggregation, and development of protein deposition disorders. It is devoted to the general questions of conformational disorders and includes discussion of involvement of such common factors as molecular chaperones, oxidative damage, proteasome, glycosoaminoglycans, serum amyloid protein P and several others in the development of different disorders. Some experimental techniques applicable for the visualization of protein deposition in vivo and in vitro are also present.

Table of Contents

Contributors xvii
1. Structural and Conformational Prerequisites of Amyloidogenesis
Vladimir N. Uversky, Ariel Fernández, and Anthony L. Fink
1. Abstract
1(1)
2. Introduction
1(5)
3. What Kind of Defects in the Soluble Folded State Bolster the Conversion to the Amyloidogenic Phase?
6(1)
4. What Are the Conformational Prerequisites for Partially Folded Intermediates to Become the Amyloidogenic Species?
7(7)
4.1. The Requirement for Partial Unfolding: Fibrillogenesis of Globular Proteins
7(1)
4.1.1. Transthyretin
8(1)
4.1.2. β2-Microglobulin
8(1)
4.1.3. Serum Amyloid, A Protein
9(1)
4.1.4. Immunoglobulin Light Chains
9(1)
4.1.5. Insulin
9(1)
4.1.6. Human Lysozyme
10(1)
4.1.7. α-Lactalbumin
10(1)
4.1.8. Monellin
10(1)
4.2. The Requirement for Partial Folding: Fibrillogenesis of Natively Unfolded Proteins
10(1)
4.2.1. Amyloid β-Protein
11(1)
4.2.2. Tau Protein
11(1)
4.2.3. α-Synuclein
11(1)
4.2.4. Amylin
12(1)
4.2.5. Prothymosin α
12(1)
4.3. Conformational Prerequisites for Amyloidogenesis: Why a Premolten Globule?
12(2)
5. Concluding Remarks
14(1)
6. Abbreviations
14(1)
References
14(7)
2. The Generic Nature of Protein Folding and Misfolding
Christopher M. Dobson
1. Abstract
21(1)
2. Introduction
21(1)
3. The Universal Mechanism of Protein Folding
22(2)
4. Protein Folding and Misfolding in the Cellular Environment
24(2)
5. The Generic Nature of Amyloid Formation
26(4)
6. Common Features of Protein Self-Assembly
30(2)
7. Generic Aspects of Misfolding Diseases
32(2)
8. Common Strategies for Therapeutic Intervention
34(2)
9. Concluding Remarks
36(1)
10. Abbreviations
36(1)
Acknowledgments
36(1)
References
37(6)
3. Relative Importance of Hydrophobicity, Net Charge, and Secondary Structure Propensities in Protein Aggregation
Fabrizio Chiti
1. Abstract
43(1)
2. Introduction
43(1)
3. Importance of Hydrophobicity in Protein Aggregation
44(17)
3.1. Analysis of Four Representative Cases
44(1)
3.1.1. Αβ
44(1)
3.1.2. α-Syn
45(1)
3.1.3. PHF43 (Fragment from τ)
46(1)
3.1.4. AcP
46(1)
3.2. Protein Aggregation Is Promoted by Hydrophobic Regions of a Sequence
46(1)
4. Importance of Charge in Protein Aggregation
47 (1)
4.1. Reduction of the Net Charge of a Protein Increases Its Propensity to Aggregate
47(1)
4.2. Aggregation Is Favored by Macromolecules with an Opposite Charge
48 (1)
4.3. Charge Interactions Modulate, Rather Than Promoting Specifically, Aggregation
49(1)
5. Importance of the Propensity to a Form Secondary Structure in Protein Aggregation
50 (1)
5.1. Sequences with a High Propensity to Form β-Structures Are Highly Amyloidogenic
50 (1)
5.2. Sequences with a High Propensity to Form α-Helical Structures Exhibit Poor Amyloidogenicity
51(1)
6. Mutations Modulate Aggregation as a Result of Their Effects on Simple Physicochemical Determinants
52(1)
7. Amino Acid Sequences Have Evolved to Take into Account the Influence of Hydrophobicity, Charge, and β-Sheet Propensity in Protein Aggregation
53(1)
8. Other Factors Involved in Protein Aggregation
54(1)
9. Is Protein Aggregation Driven by Specific Sequences?
55(1)
10. Future Perspectives
55(1)
11. Abbreviations
56(1)
References
56(5)
4. Cytotoxic Intermediates in the Fibrillation Pathway: Αβ Oligomers in Alzheimer's Disease as a Case Study
William L. Klein
1. Abstract
61(1)
2. AD Is a Dementia Involving the Fibrillogenic A13 Peptide
61(2)
3. Why the Fibril-Based Cascade Hypothesis Unraveled: A Singular Illustration with a Transgenic Mouse AD Model
63(1)
4. If Not Fibrils, What? Discovery of Αβ's Hidden Toxins
63(1)
5. Oligomers Have Profound Neurological Impact, Accounting for Reversibility of Memory Loss
64(1)
6. How Oligomers Attack Neurons—A Molecular Mechanism for Why AD Is Specific for Memory Loss
65(1)
7. Immediate Consequences of Oligomer Binding: Signal Transduction Targets
66(1)
8. Cascading Consequences—Can Oligomer-Induced Synapse Dysfunction Lead to Synapse Destruction and Neuron Death?
67(1)
9. In Vivo Experimental Support for Synaptotoxic Oligomers: Data from Mouse Models of Early AD
67(1)
10. Clinical Validation—Oligomers in Human Brain, Elevated up to 70-Fold in AD
68(1)
11. New "Oligomer-Driven" Amyloid Hypothesis
69(1)
12. Mechanisms of Αβ Oligomerization and Fibrillogenesis
69(2)
13. Pathogenic Αβ Oligomers—First of Many? All Proteins Likely Have the Capacity to Oligomerize
71(2)
14. Therapeutics and Diagnostics—New Strategies
73(2)
15. Abbreviations
75(1)
Acknowledgments
75(1)
Potential Conflicts
75(1)
References
75(8)
5. Glycosaminoglycans, Proteoglycans, and Conformational Disorders
Gregory J. Cole and I.-Hsuan Liu
1. Abstract
83(1)
2. Biochemical Properties of Proteoglycans and Glycosaminoglycans
83(2)
3. Neurodegenerative Diseases Are Protein Conformational Disorders
85(7)
3.1. AD
86(3)
3.2. PD
89(2)
3.3. Prion Diseases
91(1)
4. Proteoglycans Contribute to Protein Misfolding in Conformational Protein Disorders Outside the Nervous System
92(2)
4.1. Type 2 Diabetes
92(1)
4.2. Inflammation-Associated AA Amyloidosis
93(1)
4.3. β2-Microglobulin-Related Amyloidosis
94(1)
5. Conclusions
94(1)
6. Abbreviations
95(1)
References
95(6)
6. Apolipoproteins in Different Amyloidoses
Marcin Sadowski and Thomas Wisniewski
1. Abstract
101(1)
2. Introduction
101(2)
3. Molecular Characteristic of Apolipoproteins Involved in Amyloidoses
103(1)
3.1. Apolipoprotein A
103(1)
3.2. Apolipoprotein E
103(1)
3.3. Apolipoprotein J
103(1)
4. Role of Apolipoproteins in Pathological Mechanism of AD Amyloidosis
104(5)
4.1. Effect of Apo E on Αβ Fibrillization and Deposition
105 (2)
4.2. Role of Apolipoproteins in ΑΒ Trafficking Across the BBB, in the Serum and in the CSF
107(1)
4.3. Apolipoproteins and Neuronal Pathology in AD
108(1)
4.4. Apolipoproteins and Cerebral Amyloid Angiopathy
108(1)
5. Apolipoproteins in Prion Diseases
109(1)
6. Apolipoproteins in Other Amyloidoses
110(1)
7. Apolipoproteins as a Substrate of Amyloid Fibrils
111(1)
8. Apolipoproteins as a Therapeutic Target in Amyloidoses
111(1)
9. Abbreviations
112(1)
References
113(10)
7. Oxidative Stress and Protein Deposition Diseases
Joseph R. Mazzulli, Roberto Hodara, Summer Lind, and Harry Ischiropoulos
1. Abstract
123(1)
2. Introduction to Oxidative and Nitrative Stresses
123(2)
3. Oxidative and Nitrative Stresses in Neurodegenerative Diseases with Protein Deposits
125(5)
3.1. Alzheimer's Disease
126 (1)
3.1.1. Oxidative Modifications of Tau Are Associated with Protein Deposition and Neurodegeneration
126(1)
3.2. Oxidative Protein Deposition in Transmissible Spongiform Encephalopathies
127(1)
3.3. Oxidative Stress and Synucleinopathies
128(2)
4. Abbreviations
130(1)
References
130(7)
8. Chaperone and Conformational Disorders
8.1. Chaperone Suppression of Aggregated Protein Toxicity
Jennifer L. Wacker and Paul J. Muchowski
1. Abstract
137(1)
2. Protein Folding and Misfolding
137(1)
3. Cellular Quality Control
138(1)
3.1. The Molecular Chaperones
138(1)
3.2. The Ubiquitin Proteasome
139(1)
4. Mutations in Molecular Chaperones Responsible for Human Disease
140(1)
5. Protein Misfolding Diseases
140(1)
5.1. AD
140(1)
5.2. PD
141(1)
5.3. ALS
141(1)
5.4. Polyglutamine Expansion Diseases
142(1)
6. Protein Aggregates: A Common Denominator of Neurodegenerative Disease
142(1)
7. Molecular Chaperones: Key Regulators of Protein Aggregation and Toxicity
143(1)
7.1. AD and Related Dementias
145(1)
7.2. PD
148(1)
7.3. FALS
150(1)
7.4. Polyglutamine Expansion Diseases
150(5)
8. Chaperones as a Potential Drug Target
155(1)
8.1. Chemical Chaperones
155(1)
8.2. Drugs That Upregulate Chaperone Expression
155(1)
9. Abbreviations
156(1)
References
156(9)
8.2. Mechanisms of Active Solubilization of Stable Protein Aggregates by Molecular Chaperones
Pierre Goloubinoff and Anat Peres Ben-Zvi
1. Abstract
165(1)
2. Choosing Between Native Folding and Misfolding
165(1)
3. Many Molecular Chaperones Can Prevent Protein Aggregation
166(1)
4. Some ATPase Chaperones Can Solubilize and Reactivate Stable Protein Aggregates
167(1)
5. Prevention of Aggregation Is Not Required for Chaperone-Dependent Protein Refolding
167(1)
6. ATPase Chaperones Can Unfold Misfolded Proteins
167(1)
7. Ring-Shaped Chaperone Oligomers Can Use Power Strokes to Actively Unfold Aggregates
168(1)
8. Individual Chaperone Monomers Can Use Random Motions to Actively Unfold Aggregates
169(1)
9. Conclusion: The Successive Lines of Defense Against Protein Aggregation and Diseases
170(1)
10. Abbreviation
171(1)
Acknowledgments
171(1)
References
171(4)
9. The Aggresome: Proteasomes, Inclusion Bodies, and Protein Aggregation
Jennifer A. Johnston
1. Abstract
175(1)
2. Introduction
175(1)
3. Characteristics of Aggresomes
176(8)
3.1. Aggresomes Are Composed of Aggregated, Undegraded Protein
177(3)
3.2. Aggresomes Can Be Ub Positive or Ub Negative
180(1)
3.3. Aggresome Formation Is an MT and Dynein–Dynactin-Dependent Process
181(1)
3.4. Aggresomes Formation at the Centrosome
182(1)
3.5. Aggresomes Are Associated with Rearrangements in IFs
183(1)
4. Examples of Aggresomes in Human Health and Disease
184(15)
4.1. Aggresomes That Form as Part of a Normal Process
185(1)
4.1.1. DALIS (Dendritic Cell Aggresome-Like Induced Structures)
185(1)
4.1.2. Glutamate Receptor Subunit 1 (GluR1) Aggresomes
186(1)
4.1.3. Stigmoid Bodies: 5-HT7 Receptors and Aromatase
187(1)
4.2. Aggresomes That Form as Part of a Disease Process
187(1)
4.2.1. Aggresomes and Viral Factories
187(1)
4.2.2. Mallory Bodies: Hepatic Disorders and Cytokeratin
188(1)
4.2.3. Retinitis Pigmentosa: Rhodopsin
190(1)
4.2.4. Desmin-Related Myopathy (DRM): αβ-Crystallin
191(1)
4.2.5. Prion Disorders: Prion Protein
192(1)
4.2.6. Bunina Bodies: ALS and SOD!
193(1)
4.2.7. Huntington's Disease: Expanded CAG Region of Huntington
194(1)
4.2.8. Charcot-Marie-Tooth Disease: Peripheral Myelin Protein 22 (PMP22)
195(1)
4.2.9. Cataracts: Connexin 50, 43
196(1)
4.2.10. Parkinson's Disease: Lewy Bodies/Parkin/α-Synuclein
197(2)
5. Mechanisms of Aggresome Formation
199(8)
5.1. Proteasome Biology: Substrate Competition
199(3)
5.2. Cellular Neurobiology: The Role of the Ub–Proteasome Pathway in Neurons
202(4)
5.3. The Biophysical Process of Fibril Formation
206(1)
6. Future Directions
207(1)
7. Abbreviations
208(1)
References
208(15)
10. Protein Aggregation, Ion Channel Formation, and Membrane Damage
Bruce L. Kagan
1. Abstract
223(1)
2. Introduction
223(2)
3. Alzheimer's Disease (Αβ)
225(2)
4. Prion (PrP) Channels
227(1)
5. Type II Diabetes Mellitus and Islet Amyloid Polypeptide (IAPP, Amylin)
228(1)
6. α-Synuclein and Parkinson's Disease
229(1)
7. Polyglutamine and Triplet Repeat Diseases
229(1)
8. Mechanisms of Membrane-Mediated Damage
230(3)
8.1. Plasma Membranes
230(1)
8.2. Mitochondrial Membranes
231(1)
8.3. Other Intracellular Membranes
232(1)
8.4. Other Amyloid Peptides
232(1)
9. Abbreviations
233(1)
References
233(6)
11. Visualization of Protein Deposits In Vivo
11.1. Congo Red Staining of Amyloid: Improvements and Practical Guide for a More Precise Diagnosis of Amyloid and the Different Amyloidoses
Reinhold P. Linke
1. Abstract
239(1)
2. Amyloidosis
239(2)
3. Identification of Amyloid Using Dyes
241(1)
3.1. Introduction
241(1)
3.2. Staining of Amyloid Before 1922
241(1)
3.3. CR as a Diagnostic Tool (Since 1922)
242(1)
3.4. Some Current Staining Protocols Using CR
243(1)
3.5. Staining of Amyloid-Like Fibrils with CR
243(1)
3.6. CR as a Fluorochrome
244(1)
3.7. Thioflavin
245(1)
3.8. Other Dyes and CR Analogues
245(1)
4. The Chemical Structure of CR and Some Properties
246(1)
4.1. History and Chemistry
246(1)
4.2. Characteristics of CR Crystals
247(1)
4.3. Concerning the Value of the Green Polarization Color
247(1)
4.4. Colored Anisotropy After Binding of CR
248(1)
4.5. Mechanism of CR Binding to Amyloids
248(1)
5. Concerning the Specificity of CR
249(1)
6. Concerning the Practical Use of CR
250(1)
6.1. The Quality of Equipment
250(1)
6.2. The Quality and Kind of the Biopsy
251(1)
6.3. The Size of the Biopsy and the Sampling Error
251(1)
6.4. The Quality of Tissue Sections and Minute Amyloid Deposits
251(1)
6.5. The Quality of Staining
251(1)
6.6. Imbibition of Serum and Tissue Proteins
252(1)
6.7. Relative Insensitivity of the Conventional CR Staining Procedure
253(1)
6.8. Increased Sensitivity of the CR Procedure by Immunohistochemistry (CRIC)
253(1)
6.9. Increased Sensitivity Using CRF
254(1)
6.10. Concerning the Reciprocal Properties of Sensitivity and Specificity
254(1)
6.11. The Polarization Shadow
255(1)
6.12. Inconclusiveness of a Negative Amyloid Diagnosis
255(1)
6.13. Precision of the Diagnosis and Courtesy Toward the Clinician
255(1)
7. Chemical Identification of Amyloidosis
255(1)
7.1. Before the Chemical Identification
255(1)
7.2. Chemical Classification
256(1)
7.3. Amyloid Typing in Clinicopathologic Practice
256(1)
7.4. Immunohistochemical Classification of Amyloids
256(1)
7.5. Microextraction Followed by an Amino Acid Sequence
259(1)
8. Advice for the Immunohistochemical Classification of Amyloids
260(1)
8.1. Introduction
260(1)
8.2. Approved Antibodies and Controls
260(1)
8.3. Sets of Antibodies
261(1)
8.4. Prestaining with CR
261(1)
8.5. Serial Sections
261(1)
8.6. Other Amyloid Components
262(1)
9. From Bench to Bedside: An Algorithm for a Reliable Diagnosis
262(1)
9.1. Classifications Before the Chemical Nature of Amyloid Was Known
262(1)
9.2. Classification According to the Chemical Nature of Amyloid Proteins
262 (1)
9.3. An Important Remark Pointing to the Correct Hierarchy of Diagnosing Amyloidosis
264(1)
9.4. Diagnosing Amyloidosis Correctly with Respect to Therapy
264(1)
10. Quantification of Amyloid
265(1)
11. Novel Techniqes in Amyloid Research
266(1)
12. Abbreviations
267(1)
Acknowledgments
267(1)
References
267(10)
11.2. Immunohistological Study of Experimental Murine AA Amyloidosis
Mie Kuroiwa, Kimiko Aoki, and Naotaka Izumiyama
1. Abstract
277(1)
2. Introduction
277(1)
3. Amyloid Induction
278(1)
4. Detection of Components of Amyloid Fibrils and Macrophages
279(1)
4.1. Detection of F4/80 Macrophages with Light Microscopy
279(1)
4.2. Detection with Fluorescence Microscopy
279(1)
4.3. Detection with Confocal Laser-Scanning Microscopy
279(1)
4.4. Detection with Electron Microscopy
280(1)
5. Induction of Amyloid Deposition in the Marginal Zone
280(1)
6. Time-kinetic Detection of Amyloid Components and Macrophages by Double Immunofluorescence Method
280(1)
7. Formation of Amyloid Fibrils
281(1)
8. Resorption of Amyloid Fibrils
282(1)
9. Abbreviations
282(1)
References
282(5)
12. Visualization of Protein Deposits In Vitro
12.1. Reporters of Amyloid Structure
Harry LeVine, III
1. Abstract
287(1)
2. Common Elements of Amyloid Fibrils
287(1)
3. Probes in Which Amyloid Fibrils Induce Changes
288(1)
3.1. Probes of Fibril Formation
288(1)
3.2. Probes of Soluble Al3 Monomer Conformation
289(1)
4. Tight Binding Probes for Amyloid Imaging
290(1)
4.1. Distinction Between Plaques and Neurofibrillary Tangles
290(1)
4.2. Binding Proteins
290(1)
4.3. Small Molecule Binders
291(1)
5. The Phenomenon of Cognate Peptide Recognition
292(1)
6. Conformation-Dependent Antibodies
293(1)
6.1. Clinical Utility
293(1)
6.2. Conformational Epitopes
294(1)
6.3. Antifibrillar Antibodies
294(1)
6.4. Antioligomer Antibodies
295(1)
7. Abbreviations
296(1)
Acknowledgments
296(1)
References
296(7)
12.2. Three-Dimensional Structural Analysis of Amyloid Fibrils by Electron Microscopy
Sara Cohen-Krausz and Helen R. Saibil
1. Abstract
303(1)
2. Introduction: Structural Studies
303(1)
3. Amyloid Fibril Structure and the Cross-13 Fold
303(2)
4. EM Methods for Amyloid
305(1)
4.1. Structural Information Depends on the Type of EM Sample Preparation
305(1)
4.2. 3D Reconstruction from Electron Micrographs
306(1)
4.3. Sorting Out Structural Variations by Image Analysis
307(1)
5. Results of EM Studies
308(1)
5.1. Protofilament Arrangement and Fibril Morphology
308 (1)
5.1.1. The β-Strands in Amyloid Fibrils Stack with a Slight, Left-Handed Twist
309(1)
5.2. Prion Amyloid Models from Crystalline Arrays
309(1)
5.3. The Structure of Intermediate Oligomers—The Toxic Agent?
310(1)
6. Prospects for Fibril Structure Determination
311(1)
7. Abbreviations
311(1)
References
311(4)
12.3. Atomic Force Microscopy
Justin Legleiter and Tomasz Kowalewski
1. Abstract
315(1)
2. Introduction
315(1)
3. AFM
316(1)
4. Studies of Αβ Peptide Aggregation and Morphology
317(1)
4.1. Αβ Aggregation and Fibrillization
317(1)
4.1.1. Commonly Observed Αβ Morphologies
317(1)
4.1.2. Seeding and Amyloidogenic Peptide Fragments
318(1)
4.2. Factors Modulating Αβ Aggregation
319(1)
4.2.1. Role of Solution Conditions
319(1)
4.2.2. Interactions of All with Lipids
320(1)
4.2.3. Other Factors Affecting Αβ Aggregation
322(2)
5. Studies of α-Syn Aggregation and Morphology
324(1)
5.1. α-Syn Aggregation and Fibrillization
324(1)
5.1.1. Fibril Assembly Pathway
324 (1)
5.1.2. The Exploration of α-Syn Sequence: Studies of Mutants and Fragments
324(3)
5.2. Factors Modulating α-Syn Aggregation
327(1)
5.2.1. The Role of pH
327(1)
5.2.2. Interactions of α-Syn with Lipids
327(1)
5.2.3. Other Factors Affecting α-Syn Aggregation
328(2)
6. Studies of Other Amyloid-Forming Peptides
330(1)
7. Conclusions
331(1)
8. Abbreviations
331(1)
References
331(4)
12.4. Direct Observation of Amyloid Fibril Growth Monitored by Total Internal Reflection Fluorescence Microscopy
Tadato Ban and Yuji Goto
1. Abstract
335(1)
2. Introduction
335(1)
3. Experimental Procedures
336(1)
3.1. Fluorescence Microscopy
336(1)
3.2. Direct Observation of Amyloid Fibrils
337(1)
3.3. Time-Lapse Observation of Amyloid Fibrils
337(1)
4. Results and Discussion
337(1)
4.1. ThT Observation of β2-m Amyloid Fibrils
337(1)
4.2. Kinetics of Fibril Extension
339(1)
4.3. Medin Fragment and Αβ(1-40)
340(1)
5. Conclusion
341(1)
6. Abbreviations
342(1)
Acknowledgments
342(1)
References
342(5)
13. Animal and Cell Models of Human Neurodegenerative Disorders
13.1. Drosophila and C. elegans Models of Human Age-Associated Neurodegenerative Diseases
Julide Bilen and Nancy M. Bonini
1. Abstract
347(1)
2. Introduction
347(1)
3. Modeling Human Polyglutamine Diseases
348(1)
3.1. Human Polyglutamine Diseases
348(1)
3.2. Modeling Polyglutamine Diseases in Drosophila melanogaster
349(1)
3.3. Lessons from Fly Models: Suppressors and Enhancers of PolyQ Toxicity
350(1)
3.3.1. Chaperones as Suppressors of PolyQ Toxicity
350(1)
3.3.2. Transcriptional Activity Modulates PolyQ Toxicity
351(1)
3.3.3. Pathogenic PolyQ Protein Causes Axonal Transport Defects
351(1)
3.3.4. Additional Modifiers of PolyQ Pathogenicity
352(1)
3.4. C. elegans Models of Polyglutamine Disease
353(1)
3.5. Lessons from Nematode Models: Suppressors and Enhancers
353(1)
4. Modeling Noncoding Trinucleotide Repeat Diseases
354(1)
4.1. Noncoding Trinucleotide Repeat Diseases
354(1)
4.2. Modeling Fragile X in the Fly
354(1)
4.3. A Model for SCA8
355(1)
5. Modeling PD
355(1)
5.1. PD
355(1)
5.2. α-Synuclein Models for Dominant PD in the Fly
356(1)
5.3. Parkin Models for Recessive Parkinsonism in the Fly
357(1)
5.4. Fly Modifiers of PD
357(1)
5.5. Modeling PD in C. elegans
358(1)
6. Modeling Alzheimer's and Related Diseases
359(1)
6.1. Alzheimer's and Related Diseases
359(1)
6.2. Modeling AD with Αβ and APP in Drosophila
359(1)
6.3. Tau Models in Drosophila
360(1)
6.4. Modifiers of AD and Taupathies in the Fly
361(1)
6.5. Modeling Alzheimer's and Related Diseases in C. elegans
361(1)
6.6. C. elegans Modifiers of AD Phenotypes
362(1)
7. Future Directions
362(1)
8. Abbreviations
363(1)
Acknowledgments
364(1)
References
364(7)
13.2. Genetically Engineered Mouse Models of Neurodegenerative Disorders
Eliezer Masliah and Leslie Crews
1. Abstract
371(1)
2. Introduction
371(3)
3. Alzheimer's Disease and Cerebrovascular Amyloidosis
374(1)
3.1. Modeling the Pathogenesis of AD in Animals
374(1)
3.2. APP tg Models of AD
374(1)
3.3. Behavioral Deficits and Neurodegeneration in APP tg Models of AD
377(1)
3.4. Crosses of APP tgs with Other Lines
378(1)
3.5. Models of Cerebrovascular Amyloidosis
379(1)
3.6. Neurofibrillary Pathology in tg Models of AD
380(1)
4. Fronto-temporal Dementias and Tauopathies
381(1)
4.1. Introduction to the Pathogenesis of Tauopathies in Animal Models
381(1)
4.2. Transgenic Models of Neurofibrillary Tangle Disease
381(3)
5. Lewy Body Dementia and PD
384(1)
5.1. Role of α-Synuclein in the Pathogenesis of LBD
384(1)
5.2. α-Synuclein tg Models of LBD
385(1)
5.3. Modeling Other Environmental and Genetic Factors in LBD tg Models
388(2)
6. Amyotrophic Lateral Sclerosis
390(1)
7. Neurodegenerative Disorders with Trinucleotide Repeats
391 (1)
7.1. Introduction to the Pathogenesis of Trinucleotide Repeat Disorders in Animal Models
391(1)
7.2. Models of HD
391(1)
7.3. Models of Noncoding Trinucleotide Repeat Disorders
392(1)
8. Conclusions
393(1)
9. Abbreviations
393(2)
Acknowledgments
395(1)
References
395(14)
Index 409

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