Robert Crichton, Roberta Ward

Metal-Based Neurodegeneration

From Molecular Mechanisms to Therapeutic Strategies

• Gebundenes Buch

Produktbeschreibung

This exciting new edition examines the causes of debilitating neurological disorders such as Parkinson's disease, CJD, and Huntington's disease, and gives indications of the prospects for therapy based on the understanding of molecular defects involved in these diseases. Looking at each specific neurological disorder in turn, the book outlines the role of metals in human biology, particularly in the brain, and explores tools for testing potential therapeutic strategies. It concludes with an overview of the potential of both chelation and antioxidant therapy, and outlines some perspectives for the future.

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Neurodegenerative diseases of the human brain appear in various forms, resulting in disorders of movement and coordination, cognitive deterioration and psychiatric disturbances. Many of the key factors leading to neurodegenerative diseases are similar, including the dysfunction of metal ion homeostasis, redox-active metal ions generating oxidative stress, and intracellular inclusion bodies.

Metal-based Neurodegeneration presents a detailed survey of the molecular origins of neurodegenerative diseases. Each chapter is dedicated to a specific disease, presenting the latest scientific findings, including details of their biochemical actors (proteins or peptides), their normal and pathological conformations, and a description of the diseases characteristics, with an emphasis on the role of metal-induced oxidative stress, which can result in the production of intracellular aggregates of target proteins and peptides.

Topics covered include:
Brain function, physiology and the blood-brain barrier
Immune system and neuroinflammation
Aging and mild cognitive impairment, MCI
Parkinson's Disease
Alzheimer's Disease
Creutzfelt-Jakob and related prion diseases
Alcoholic Brain Damage
Therapeutic strategies to combat the onset and progression of neurological diseases

This extensively updated, full colour, second edition of Metal-based Neurodegeneration is an essential text for research scientists and clinicians working in gerontology, neuropathology, neurochemistry, and metalloprotein mechanisms.

Produktdetails

• Verlag: Wiley & Sons
• Artikelnr. des Verlages: 1W119977140
• 2. Aufl.
• Seitenzahl: 438
• Erscheinungstermin: November 2013
• Englisch
• Abmessung: 251mm x 174mm x 27mm
• Gewicht: 1004g
• ISBN-13: 9781119977148
• ISBN-10: 1119977142
• Artikelnr.: 36875247

Autorenporträt

Robert Crichton and Roberta Ward, Unit of Biochemistry, Université Catholique de Louvain, Belgium

Inhaltsangabe

Preface xi 1 Brain Function, Physiology and the Blood-Brain Barrier 1 1.1
Introduction - An Overview of Brain Structure and Function 1 1.1.1 The
Forebrain 1 1.1.2 The Midbrain 4 1.1.3 The Hindbrain 4 1.2 The Cell Types
of the Brain 7 1.2.1 Neurons 7 1.2.2 Glial Cells 11 1.3 The Blood-Brain
Barrier 19 References 21 2 Role of Metal Ions in Brain Function, Metal
Transport, Storage and Homoeostasis 23 2.1 Introduction - The Importance of
Metal Ions in Brain Function 23 2.2 Sodium, Potassium and Calcium Channels
and Pumps 24 2.3 Calcium and Signal Transduction 30 2.4 Zinc, Copper and
Iron 37 2.5 Zinc 37 2.6 Copper 41 2.7 Iron 42 References 48 3 Immune System
and Neuroinflammation 51 3.1 General Introduction 51 3.1.1 Innate Immune
Response and Neuroinflammation 51 3.1.2 Adaptive Immunity and
Neuroinflammation 58 3.1.3 Adaptive Immunity and Neuroinflammation 59 3.1.4
Other Factors Contributing to Neuroinflammation 60 3.1.5 Anti-inflammatory
Systems to Regulate Microglia Activation 60 3.2 Apoptosis 63 3.2.1 Iron
Metabolic Regulators and Effectors during Inflammation 68 References 72 4
Oxidative Stress in Neurodegenerative Diseases 75 4.1 Introduction - The
Oxygen Paradox 75 4.2 Reactive Oxygen Species 76 4.3 Reactive Nitrogen
Species 79 4.4 Cellular Defence Mechanisms against Oxidative Stress 82 4.5
ROS, RNS and Cellular Signalling 87 4.6 ROS, RNS and Oxidative Damage 91
4.7 Epigenetics 97 4.7.1 Histone Modifications 100 4.8 Misfolded Protein
Aggregates in Neurodegenerative Diseases 101 4.9 The Amyloid State -
Structure, Nucleation and Aggregation 102 References 107 5 Ageing and Mild
Cognitive Impairment (MCI) 111 5.1 Introduction 111 5.1.1 Gene Involvement
and Epigenetics 112 5.1.2 DNA Methylation 112 5.1.3 Histone
Post-translational Modifications 113 5.2 Prevalence of MCI 114 5.2.1 MCI
Presentation 114 5.3 Brain Regions Involved 115 5.3.1 Neurochemical
Observations 116 5.3.2 Factors Involved in the Ageing Process 117 5.3.3
Mitochondria and the Ageing Process 117 5.3.4 Free Radical Theory of Ageing
118 5.3.5 Iron, Copper and Zinc in Ageing 119 5.3.6 Risk Factors for
Cognitive Decline 121 5.3.7 APOe4 Isoforms and MCI 122 5.3.8 Ageing and
Immunity 122 5.4 Proteostasis 126 5.5 Conclusion 127 References 128 6
Parkinson's Disease 131 6.1 Risk Factors for PD 131 6.2 Genetics of PD 134
6.3 SNCA 135 6.4 LRRK2 135 6.5 Parkin 135 6.6 DJ-1 135 6.7 PINK1:
PTEN-Induced Kinase 136 6.8 Epigenetics 136 6.9 miRNA 136 6.10 Proteins
Involved in PD 137 6.11 Synucleins 137 6.12 LRRK2 or PARK 8 142 6.13 PINK1
or PTEN-Induced Putative Kinase 1, PARK6 143 6.14 Parkin, PARK2 144 6.15
Synphilin-1 146 6.16 UCHL 1, Park 5 147 6.17 DJ-1, PARK 7 147 6.18 Metal
Involvement in Parkinson's Disease 148 6.18.1 Iron 148 6.18.2 Zinc 153
6.18.3 Copper 154 6.19 Neurotransmitters Involved in PD 154 6.20
Mitochondrial Dysfunction 156 6.21 PD and Inflammation 156 6.22 Receptors
Involved in the Inflammatory Response 159 6.22.1 Toll-Like Receptors 159
6.22.2 Glucocorticoid Receptor, GR 159 6.22.3 CD200/CD200R 160 6.22.4
Vitamin D Receptor (VDR) 160 6.22.5 Peroxisome Proliferators-Activated
Receptors 161 6.23 Oxidative Stress and PD 161 References 163 7 Alzheimer's
Disease 169 7.1 Introduction 169 7.2 Epidemiology and Risk Factors for AD
171 7.3 Genetics of AD 173 7.3.1 Epigenetics 174 7.4 Proteins Involved in
Alzheimer's Disease 175 7.5 Metal Involvement in Alzheimer's Disease 179
7.6 Zinc Homoeostasis in AD 181 7.7 Copper Homoeostasis in AD 181 7.8 Iron
Homoeostasis in AD 183 7.9 Neurotransmitters Involved in AD 185 7.9.1
Acetyl choline 185 7.9.2 Glutamate 187 7.10 Mitochondrial Function in
Alzheimer's Disease 189 7.11 Neuroinflammation and AD 191 7.12 Oxidative
Stress 191 References 195 8 Huntington's Disease and Polyglutamine
Expansion Neurodegenerative Diseases 203 8.1 Introduction 203 8.2 An
Overview of Trinucleotide Expansion Diseases 204 8.3 Poly-Q Diseases 204
8.4 Poly-Q Protein Aggregation and Poly-Q Disease Pathogenesis 208 8.5
Huntington's Disease 211 8.6 Other Poly-Q Disease Proteins 215 8.7
Spinocerebellar Ataxias 218 References 221 9 Friedreich's Ataxia and
Diseases Associated with Expansion of Non-Coding Triplets 227 9.1 Incidence
and Pathophysiology of Friedreich's Ataxia 227 9.2 Molecular Basis of the
Disease: Triplet Repeat Expansions 228 9.3 Molecular Basis of the Disease:
Frataxin and Its Role in Iron Metabolism 230 9.4 Other Diseases Associated
with Expansion of Non-Coding Triplets 233 References 236 10
Creutzfeldt-Jakob and Other Prion Diseases 239 10.1 Introduction 239 10.2 A
Brief History of Prion Diseases 240 10.3 Structural Aspects of the Cellular
Form of PrPC 241 10.4 'Prion' or 'Protein-Only' Hypothesis -
Conformation-Based Prion Inheritance 244 10.5 Models of PsPC to PsPSc
Conversion 246 10.6 Formation of Prion Aggregates 248 10.7 Pathways of
Prion Pathogenesis 253 References 256 11 Amyotrophic Lateral Sclerosis 261
11.1 Introduction 261 11.2 Major Genes Involved in ALS 262 11.3 Superoxide
Dismutase and ALS 265 11.4 Contributors to Disease Mechanisms in ALS 269
11.5 Excitotoxicity and Decreased Glutamate Uptake by Astroglia 269 11.6
Endoplasmic Reticulum Stress 270 11.7 Inhibition of the Proteasome 270 11.8
Mitochondrial Damage 271 11.9 Aberrant Secretion of Mutant SOD1 271 11.10
Extracellular Superoxide Generation 271 11.11 Axonal Disorganization and
Disrupted Transport 272 11.12 Microhaemorrhages of Spinal Capillaries 272
11.13 Glial Cells in ALS 273 11.14 ALS and Apoptosis 273 11.15 Prion-Like
Phenomena in ALS 274 11.16 Conclusions 276 References 276 12 Alcoholic
Brain Damage 283 12.1 General Introduction 283 12.2 Anatomy of
Alcohol-Induced Damage 285 12.3 Genetics of Alcohol-Induced Brain Damage
286 12.3.1 Epigenetics 286 12.3.2 MicroRNAs 287 12.3.3 Genetics 288 12.4
Factors Associated with Alcohol Brain Damage 291 12.5 Factors Involved in
Alcohol-Induced Brain Damage 292 12.5.1 Neuropeptides 292 12.5.2
Neurotransmitters 293 12.5.3 Acetaldehyde 294 12.5.4 Signalling Pathways
295 12.5.5 Neuroinflammation and Alcohol 296 12.5.6 Astrocytes and Alcohol
297 12.5.7 Microglia and Alcohol 300 12.5.8 NF-kB 301 12.5.9 Toll-Like
Receptors 302 12.5.10 Oligodendrocytes and Alcohol 303 12.5.11 Alcohol and
Mitochondria 303 12.5.12 Alcoholic Brain Damage and Oxidative Stress 304
References 305 13 Other Neurological Diseases 309 13.1 Introduction 309
13.2 Wilson's and Menkes Diseases 309 13.3 Neurodegeneration with Brain
Iron Accumulation 316 13.4 Aceruloplasminaemia 316 13.5 Neuroferritinopathy
318 13.6 Other Neurodegenerative Disorders with Brain Iron Accumulation 320
13.7 Multiple Sclerosis 323 13.8 HIV-Associated Neurocognitive Disorder 329
References 332 14 Therapeutic Strategies to Combat the Onset and
Progression of Neurological Diseases 337 14.1 Introduction 337 14.2
Chelation of Excessive Metal Ions 338 14.2.1 Chelation in Parkinson's
Disease 341 14.2.2 Chelation Therapy in AD 341 14.2.3 Chelation in
Friedreich Ataxia 343 14.3 Ageing and Cognitive Decline 344 14.3.1
Saturated/Unsaturated Fat Intake 344 14.3.2 Berries 345 14.3.3 Creatine
Supplementation 346 14.3.4 Sirtuins 347 14.3.5 Immunity 347 14.3.6
Mitochondria Mutations 348 14.4 Parkinson's Disease 348 14.4.1
Nutraceutical 349 14.4.2 NASIs and COX2 Inhibitors 351 14.4.3 Physical
Exercise 351 14.4.4 Dopamine Agonists 352 14.4.5 Monoamine Oxidase
Inhibitors 354 14.4.6 L-DOPA 355 14.4.7 Mitochondria and PD 356 14.4.8
Sirtuins 356 14.4.9 Creatine 357 14.4.10 CoQ10 358 14.4.11 Surgical
Treatment for PD 358 14.5 Alzheimer's Disease 359 14.5.1 Epigenetic
Modifications 359 14.5.2 Sirtuins 359 14.5.3 Tau Kinase Inhibitors 359
14.5.4 Neurotransmitters 360 14.5.5 Anti-inflammatory Drugs 360 14.5.6
Strategies to Remove Ab 360 14.5.7 Ab Immunotherapy 363 14.6 Huntington's
Disease and Other Poly-Q Diseases 364 14.7 Friedreich's Ataxia and Other
Non-Coding Nucleotide Repeat Diseases 367 14.8 Creutzfeld-Jakob and Other
Prion Diseases 370 14.9 Amyotrophic Lateral Sclerosis 372 14.10 Alcohol
Abuse 373 14.11 Other Neurological Diseases 378 14.11.1 Wilson's and Menkes
Diseases 378 14.11.2 Neurodegeneration with Brain Iron Accumulation 379
14.12 Multiple Sclerosis 381 14.13 HIV-Associated Neurocognitive Disorder
386 References 387 15 Concluding Remarks 395 15.1 New Innovative
Therapeutics 400 15.1.1 Stem Cells 402 15.2 Biochemical Biomarkers of
Neurodegenerative Diseases 404 15.2.1 Parkinson's Disease 404 15.2.2
Alzheimer's Disease 404 15.2.3 Alcohol Brain Damage 405 15.2.4 Epilogue 405
References 406 Index