{"product_id":"metalbased-neurodegeneration-9781119977148","title":"MetalBased Neurodegeneration","description":"\u003cb\u003eBook Synopsis\u003c\/b\u003e\u003cbr\u003eThis 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.\u003cbr\u003e\u003cbr\u003e\u003cb\u003eTable of Contents\u003c\/b\u003e\u003cbr\u003e\u003cp\u003ePreface xi\u003c\/p\u003e \u003cp\u003e1 Brain Function, Physiology and the Blood–Brain Barrier 1\u003c\/p\u003e \u003cp\u003e1.1 Introduction – An Overview of Brain Structure and Function 1\u003c\/p\u003e \u003cp\u003e1.1.1 The Forebrain 1\u003c\/p\u003e \u003cp\u003e1.1.2 The Midbrain 4\u003c\/p\u003e \u003cp\u003e1.1.3 The Hindbrain 4\u003c\/p\u003e \u003cp\u003e1.2 The Cell Types of the Brain 7\u003c\/p\u003e \u003cp\u003e1.2.1 Neurons 7\u003c\/p\u003e \u003cp\u003e1.2.2 Glial Cells 11\u003c\/p\u003e \u003cp\u003e1.3 The Blood–Brain Barrier 19\u003c\/p\u003e \u003cp\u003eReferences 21\u003c\/p\u003e \u003cp\u003e2 Role of Metal Ions in Brain Function, Metal Transport, Storage and Homoeostasis 23\u003c\/p\u003e \u003cp\u003e2.1 Introduction – The Importance of Metal Ions in Brain Function 23\u003c\/p\u003e \u003cp\u003e2.2 Sodium, Potassium and Calcium Channels and Pumps 24\u003c\/p\u003e \u003cp\u003e2.3 Calcium and Signal Transduction 30\u003c\/p\u003e \u003cp\u003e2.4 Zinc, Copper and Iron 37\u003c\/p\u003e \u003cp\u003e2.5 Zinc 37\u003c\/p\u003e \u003cp\u003e2.6 Copper 41\u003c\/p\u003e \u003cp\u003e2.7 Iron 42\u003c\/p\u003e \u003cp\u003eReferences 48\u003c\/p\u003e \u003cp\u003e3 Immune System and Neuroinflammation 51\u003c\/p\u003e \u003cp\u003e3.1 General Introduction 51\u003c\/p\u003e \u003cp\u003e3.1.1 Innate Immune Response and Neuroinflammation 51\u003c\/p\u003e \u003cp\u003e3.1.2 Adaptive Immunity and Neuroinflammation 58\u003c\/p\u003e \u003cp\u003e3.1.3 Adaptive Immunity and Neuroinflammation 59\u003c\/p\u003e \u003cp\u003e3.1.4 Other Factors Contributing to Neuroinflammation 60\u003c\/p\u003e \u003cp\u003e3.1.5 Anti-inflammatory Systems to Regulate Microglia Activation 60\u003c\/p\u003e \u003cp\u003e3.2 Apoptosis 63\u003c\/p\u003e \u003cp\u003e3.2.1 Iron Metabolic Regulators and Effectors during Inflammation 68\u003c\/p\u003e \u003cp\u003eReferences 72\u003c\/p\u003e \u003cp\u003e4 Oxidative Stress in Neurodegenerative Diseases 75\u003c\/p\u003e \u003cp\u003e4.1 Introduction – The Oxygen Paradox 75\u003c\/p\u003e \u003cp\u003e4.2 Reactive Oxygen Species 76\u003c\/p\u003e \u003cp\u003e4.3 Reactive Nitrogen Species 79\u003c\/p\u003e \u003cp\u003e4.4 Cellular Defence Mechanisms against Oxidative Stress 82\u003c\/p\u003e \u003cp\u003e4.5 ROS, RNS and Cellular Signalling 87\u003c\/p\u003e \u003cp\u003e4.6 ROS, RNS and Oxidative Damage 91\u003c\/p\u003e \u003cp\u003e4.7 Epigenetics 97\u003c\/p\u003e \u003cp\u003e4.7.1 Histone Modifications 100\u003c\/p\u003e \u003cp\u003e4.8 Misfolded Protein Aggregates in Neurodegenerative Diseases 101\u003c\/p\u003e \u003cp\u003e4.9 The Amyloid State – Structure, Nucleation and Aggregation 102\u003c\/p\u003e \u003cp\u003eReferences 107\u003c\/p\u003e \u003cp\u003e5 Ageing and Mild Cognitive Impairment (MCI) 111\u003c\/p\u003e \u003cp\u003e5.1 Introduction 111\u003c\/p\u003e \u003cp\u003e5.1.1 Gene Involvement and Epigenetics 112\u003c\/p\u003e \u003cp\u003e5.1.2 DNA Methylation 112\u003c\/p\u003e \u003cp\u003e5.1.3 Histone Post-translational Modifications 113\u003c\/p\u003e \u003cp\u003e5.2 Prevalence of MCI 114\u003c\/p\u003e \u003cp\u003e5.2.1 MCI Presentation 114\u003c\/p\u003e \u003cp\u003e5.3 Brain Regions Involved 115\u003c\/p\u003e \u003cp\u003e5.3.1 Neurochemical Observations 116\u003c\/p\u003e \u003cp\u003e5.3.2 Factors Involved in the Ageing Process 117\u003c\/p\u003e \u003cp\u003e5.3.3 Mitochondria and the Ageing Process 117\u003c\/p\u003e \u003cp\u003e5.3.4 Free Radical Theory of Ageing 118\u003c\/p\u003e \u003cp\u003e5.3.5 Iron, Copper and Zinc in Ageing 119\u003c\/p\u003e \u003cp\u003e5.3.6 Risk Factors for Cognitive Decline 121\u003c\/p\u003e \u003cp\u003e5.3.7 APOe4 Isoforms and MCI 122\u003c\/p\u003e \u003cp\u003e5.3.8 Ageing and Immunity 122\u003c\/p\u003e \u003cp\u003e5.4 Proteostasis 126\u003c\/p\u003e \u003cp\u003e5.5 Conclusion 127\u003c\/p\u003e \u003cp\u003eReferences 128\u003c\/p\u003e \u003cp\u003e6 Parkinson’s Disease 131\u003c\/p\u003e \u003cp\u003e6.1 Risk Factors for PD 131\u003c\/p\u003e \u003cp\u003e6.2 Genetics of PD 134\u003c\/p\u003e \u003cp\u003e6.3 SNCA 135\u003c\/p\u003e \u003cp\u003e6.4 LRRK2 135\u003c\/p\u003e \u003cp\u003e6.5 Parkin 135\u003c\/p\u003e \u003cp\u003e6.6 DJ-1 135\u003c\/p\u003e \u003cp\u003e6.7 PINK1: PTEN-Induced Kinase 136\u003c\/p\u003e \u003cp\u003e6.8 Epigenetics 136\u003c\/p\u003e \u003cp\u003e6.9 miRNA 136\u003c\/p\u003e \u003cp\u003e6.10 Proteins Involved in PD 137\u003c\/p\u003e \u003cp\u003e6.11 Synucleins 137\u003c\/p\u003e \u003cp\u003e6.12 LRRK2 or PARK 8 142\u003c\/p\u003e \u003cp\u003e6.13 PINK1 or PTEN-Induced Putative Kinase 1, PARK6 143\u003c\/p\u003e \u003cp\u003e6.14 Parkin, PARK2 144\u003c\/p\u003e \u003cp\u003e6.15 Synphilin-1 146\u003c\/p\u003e \u003cp\u003e6.16 UCHL 1, Park 5 147\u003c\/p\u003e \u003cp\u003e6.17 DJ-1, PARK 7 147\u003c\/p\u003e \u003cp\u003e6.18 Metal Involvement in Parkinson’s Disease 148\u003c\/p\u003e \u003cp\u003e6.18.1 Iron 148\u003c\/p\u003e \u003cp\u003e6.18.2 Zinc 153\u003c\/p\u003e \u003cp\u003e6.18.3 Copper 154\u003c\/p\u003e \u003cp\u003e6.19 Neurotransmitters Involved in PD 154\u003c\/p\u003e \u003cp\u003e6.20 Mitochondrial Dysfunction 156\u003c\/p\u003e \u003cp\u003e6.21 PD and Inflammation 156\u003c\/p\u003e \u003cp\u003e6.22 Receptors Involved in the Inflammatory Response 159\u003c\/p\u003e \u003cp\u003e6.22.1 Toll-Like Receptors 159\u003c\/p\u003e \u003cp\u003e6.22.2 Glucocorticoid Receptor, GR 159\u003c\/p\u003e \u003cp\u003e6.22.3 CD200\/CD200R 160\u003c\/p\u003e \u003cp\u003e6.22.4 Vitamin D Receptor (VDR) 160\u003c\/p\u003e \u003cp\u003e6.22.5 Peroxisome Proliferators-Activated Receptors 161\u003c\/p\u003e \u003cp\u003e6.23 Oxidative Stress and PD 161\u003c\/p\u003e \u003cp\u003eReferences 163\u003c\/p\u003e \u003cp\u003e7 Alzheimer’s Disease 169\u003c\/p\u003e \u003cp\u003e7.1 Introduction 169\u003c\/p\u003e \u003cp\u003e7.2 Epidemiology and Risk Factors for AD 171\u003c\/p\u003e \u003cp\u003e7.3 Genetics of AD 173\u003c\/p\u003e \u003cp\u003e7.3.1 Epigenetics 174\u003c\/p\u003e \u003cp\u003e7.4 Proteins Involved in Alzheimer’s Disease 175\u003c\/p\u003e \u003cp\u003e7.5 Metal Involvement in Alzheimer’s Disease 179\u003c\/p\u003e \u003cp\u003e7.6 Zinc Homoeostasis in AD 181\u003c\/p\u003e \u003cp\u003e7.7 Copper Homoeostasis in AD 181\u003c\/p\u003e \u003cp\u003e7.8 Iron Homoeostasis in AD 183\u003c\/p\u003e \u003cp\u003e7.9 Neurotransmitters Involved in AD 185\u003c\/p\u003e \u003cp\u003e7.9.1 Acetyl choline 185\u003c\/p\u003e \u003cp\u003e7.9.2 Glutamate 187\u003c\/p\u003e \u003cp\u003e7.10 Mitochondrial Function in Alzheimer’s Disease 189\u003c\/p\u003e \u003cp\u003e7.11 Neuroinflammation and AD 191\u003c\/p\u003e \u003cp\u003e7.12 Oxidative Stress 191\u003c\/p\u003e \u003cp\u003eReferences 195\u003c\/p\u003e \u003cp\u003e8 Huntington’s Disease and Polyglutamine Expansion Neurodegenerative Diseases 203\u003c\/p\u003e \u003cp\u003e8.1 Introduction 203\u003c\/p\u003e \u003cp\u003e8.2 An Overview of Trinucleotide Expansion Diseases 204\u003c\/p\u003e \u003cp\u003e8.3 Poly-Q Diseases 204\u003c\/p\u003e \u003cp\u003e8.4 Poly-Q Protein Aggregation and Poly-Q Disease Pathogenesis 208\u003c\/p\u003e \u003cp\u003e8.5 Huntington’s Disease 211\u003c\/p\u003e \u003cp\u003e8.6 Other Poly-Q Disease Proteins 215\u003c\/p\u003e \u003cp\u003e8.7 Spinocerebellar Ataxias 218\u003c\/p\u003e \u003cp\u003eReferences 221\u003c\/p\u003e \u003cp\u003e9 Friedreich’s Ataxia and Diseases Associated with Expansion of Non-Coding Triplets 227\u003c\/p\u003e \u003cp\u003e9.1 Incidence and Pathophysiology of Friedreich’s Ataxia 227\u003c\/p\u003e \u003cp\u003e9.2 Molecular Basis of the Disease: Triplet Repeat Expansions 228\u003c\/p\u003e \u003cp\u003e9.3 Molecular Basis of the Disease: Frataxin and Its Role in Iron Metabolism 230\u003c\/p\u003e \u003cp\u003e9.4 Other Diseases Associated with Expansion of Non-Coding Triplets 233\u003c\/p\u003e \u003cp\u003eReferences 236\u003c\/p\u003e \u003cp\u003e10 Creutzfeldt–Jakob and Other Prion Diseases 239\u003c\/p\u003e \u003cp\u003e10.1 Introduction 239\u003c\/p\u003e \u003cp\u003e10.2 A Brief History of Prion Diseases 240\u003c\/p\u003e \u003cp\u003e10.3 Structural Aspects of the Cellular Form of PrPC 241\u003c\/p\u003e \u003cp\u003e10.4 ‘Prion’ or ‘Protein-Only’ Hypothesis – Conformation-Based Prion Inheritance 244\u003c\/p\u003e \u003cp\u003e10.5 Models of PsPC to PsPSc Conversion 246\u003c\/p\u003e \u003cp\u003e10.6 Formation of Prion Aggregates 248\u003c\/p\u003e \u003cp\u003e10.7 Pathways of Prion Pathogenesis 253\u003c\/p\u003e \u003cp\u003eReferences 256\u003c\/p\u003e \u003cp\u003e11 Amyotrophic Lateral Sclerosis 261\u003c\/p\u003e \u003cp\u003e11.1 Introduction 261\u003c\/p\u003e \u003cp\u003e11.2 Major Genes Involved in ALS 262\u003c\/p\u003e \u003cp\u003e11.3 Superoxide Dismutase and ALS 265\u003c\/p\u003e \u003cp\u003e11.4 Contributors to Disease Mechanisms in ALS 269\u003c\/p\u003e \u003cp\u003e11.5 Excitotoxicity and Decreased Glutamate Uptake by Astroglia 269\u003c\/p\u003e \u003cp\u003e11.6 Endoplasmic Reticulum Stress 270\u003c\/p\u003e \u003cp\u003e11.7 Inhibition of the Proteasome 270\u003c\/p\u003e \u003cp\u003e11.8 Mitochondrial Damage 271\u003c\/p\u003e \u003cp\u003e11.9 Aberrant Secretion of Mutant SOD1 271\u003c\/p\u003e \u003cp\u003e11.10 Extracellular Superoxide Generation 271\u003c\/p\u003e \u003cp\u003e11.11 Axonal Disorganization and Disrupted Transport 272\u003c\/p\u003e \u003cp\u003e11.12 Microhaemorrhages of Spinal Capillaries 272\u003c\/p\u003e \u003cp\u003e11.13 Glial Cells in ALS 273\u003c\/p\u003e \u003cp\u003e11.14 ALS and Apoptosis 273\u003c\/p\u003e \u003cp\u003e11.15 Prion-Like Phenomena in ALS 274\u003c\/p\u003e \u003cp\u003e11.16 Conclusions 276\u003c\/p\u003e \u003cp\u003eReferences 276\u003c\/p\u003e \u003cp\u003e12 Alcoholic Brain Damage 283\u003c\/p\u003e \u003cp\u003e12.1 General Introduction 283\u003c\/p\u003e \u003cp\u003e12.2 Anatomy of Alcohol-Induced Damage 285\u003c\/p\u003e \u003cp\u003e12.3 Genetics of Alcohol-Induced Brain Damage 286\u003c\/p\u003e \u003cp\u003e12.3.1 Epigenetics 286\u003c\/p\u003e \u003cp\u003e12.3.2 MicroRNAs 287\u003c\/p\u003e \u003cp\u003e12.3.3 Genetics 288\u003c\/p\u003e \u003cp\u003e12.4 Factors Associated with Alcohol Brain Damage 291\u003c\/p\u003e \u003cp\u003e12.5 Factors Involved in Alcohol-Induced Brain Damage 292\u003c\/p\u003e \u003cp\u003e12.5.1 Neuropeptides 292\u003c\/p\u003e \u003cp\u003e12.5.2 Neurotransmitters 293\u003c\/p\u003e \u003cp\u003e12.5.3 Acetaldehyde 294\u003c\/p\u003e \u003cp\u003e12.5.4 Signalling Pathways 295\u003c\/p\u003e \u003cp\u003e12.5.5 Neuroinflammation and Alcohol 296\u003c\/p\u003e \u003cp\u003e12.5.6 Astrocytes and Alcohol 297\u003c\/p\u003e \u003cp\u003e12.5.7 Microglia and Alcohol 300\u003c\/p\u003e \u003cp\u003e12.5.8 NF-kB 301\u003c\/p\u003e \u003cp\u003e12.5.9 Toll-Like Receptors 302\u003c\/p\u003e \u003cp\u003e12.5.10 Oligodendrocytes and Alcohol 303\u003c\/p\u003e \u003cp\u003e12.5.11 Alcohol and Mitochondria 303\u003c\/p\u003e \u003cp\u003e12.5.12 Alcoholic Brain Damage and Oxidative Stress 304\u003c\/p\u003e \u003cp\u003eReferences 305\u003c\/p\u003e \u003cp\u003e13 Other Neurological Diseases 309\u003c\/p\u003e \u003cp\u003e13.1 Introduction 309\u003c\/p\u003e \u003cp\u003e13.2 Wilson’s and Menkes Diseases 309\u003c\/p\u003e \u003cp\u003e13.3 Neurodegeneration with Brain Iron Accumulation 316\u003c\/p\u003e \u003cp\u003e13.4 Aceruloplasminaemia 316\u003c\/p\u003e \u003cp\u003e13.5 Neuroferritinopathy 318\u003c\/p\u003e \u003cp\u003e13.6 Other Neurodegenerative Disorders with Brain Iron Accumulation 320\u003c\/p\u003e \u003cp\u003e13.7 Multiple Sclerosis 323\u003c\/p\u003e \u003cp\u003e13.8 HIV-Associated Neurocognitive Disorder 329\u003c\/p\u003e \u003cp\u003eReferences 332\u003c\/p\u003e \u003cp\u003e14 Therapeutic Strategies to Combat the Onset and Progression of Neurological Diseases 337\u003c\/p\u003e \u003cp\u003e14.1 Introduction 337\u003c\/p\u003e \u003cp\u003e14.2 Chelation of Excessive Metal Ions 338\u003c\/p\u003e \u003cp\u003e14.2.1 Chelation in Parkinson’s Disease 341\u003c\/p\u003e \u003cp\u003e14.2.2 Chelation Therapy in AD 341\u003c\/p\u003e \u003cp\u003e14.2.3 Chelation in Friedreich Ataxia 343\u003c\/p\u003e \u003cp\u003e14.3 Ageing and Cognitive Decline 344\u003c\/p\u003e \u003cp\u003e14.3.1 Saturated\/Unsaturated Fat Intake 344\u003c\/p\u003e \u003cp\u003e14.3.2 Berries 345\u003c\/p\u003e \u003cp\u003e14.3.3 Creatine Supplementation 346\u003c\/p\u003e \u003cp\u003e14.3.4 Sirtuins 347\u003c\/p\u003e \u003cp\u003e14.3.5 Immunity 347\u003c\/p\u003e \u003cp\u003e14.3.6 Mitochondria Mutations 348\u003c\/p\u003e \u003cp\u003e14.4 Parkinson’s Disease 348\u003c\/p\u003e \u003cp\u003e14.4.1 Nutraceutical 349\u003c\/p\u003e \u003cp\u003e14.4.2 NASIs and COX2 Inhibitors 351\u003c\/p\u003e \u003cp\u003e14.4.3 Physical Exercise 351\u003c\/p\u003e \u003cp\u003e14.4.4 Dopamine Agonists 352\u003c\/p\u003e \u003cp\u003e14.4.5 Monoamine Oxidase Inhibitors 354\u003c\/p\u003e \u003cp\u003e14.4.6 L-DOPA 355\u003c\/p\u003e \u003cp\u003e14.4.7 Mitochondria and PD 356\u003c\/p\u003e \u003cp\u003e14.4.8 Sirtuins 356\u003c\/p\u003e \u003cp\u003e14.4.9 Creatine 357\u003c\/p\u003e \u003cp\u003e14.4.10 CoQ10 358\u003c\/p\u003e \u003cp\u003e14.4.11 Surgical Treatment for PD 358\u003c\/p\u003e \u003cp\u003e14.5 Alzheimer’s Disease 359\u003c\/p\u003e \u003cp\u003e14.5.1 Epigenetic Modifications 359\u003c\/p\u003e \u003cp\u003e14.5.2 Sirtuins 359\u003c\/p\u003e \u003cp\u003e14.5.3 Tau Kinase Inhibitors 359\u003c\/p\u003e \u003cp\u003e14.5.4 Neurotransmitters 360\u003c\/p\u003e \u003cp\u003e14.5.5 Anti-inflammatory Drugs 360\u003c\/p\u003e \u003cp\u003e14.5.6 Strategies to Remove Ab 360\u003c\/p\u003e \u003cp\u003e14.5.7 Ab Immunotherapy 363\u003c\/p\u003e \u003cp\u003e14.6 Huntington’s Disease and Other Poly-Q Diseases 364\u003c\/p\u003e \u003cp\u003e14.7 Friedreich’s Ataxia and Other Non-Coding Nucleotide Repeat Diseases 367\u003c\/p\u003e \u003cp\u003e14.8 Creutzfeld–Jakob and Other Prion Diseases 370\u003c\/p\u003e \u003cp\u003e14.9 Amyotrophic Lateral Sclerosis 372\u003c\/p\u003e \u003cp\u003e14.10 Alcohol Abuse 373\u003c\/p\u003e \u003cp\u003e14.11 Other Neurological Diseases 378\u003c\/p\u003e \u003cp\u003e14.11.1 Wilson’s and Menkes Diseases 378\u003c\/p\u003e \u003cp\u003e14.11.2 Neurodegeneration with Brain Iron Accumulation 379\u003c\/p\u003e \u003cp\u003e14.12 Multiple Sclerosis 381\u003c\/p\u003e \u003cp\u003e14.13 HIV-Associated Neurocognitive Disorder 386\u003c\/p\u003e \u003cp\u003eReferences 387\u003c\/p\u003e \u003cp\u003e15 Concluding Remarks 395\u003c\/p\u003e \u003cp\u003e15.1 New Innovative Therapeutics 400\u003c\/p\u003e \u003cp\u003e15.1.1 Stem Cells 402\u003c\/p\u003e \u003cp\u003e15.2 Biochemical Biomarkers of Neurodegenerative Diseases 404\u003c\/p\u003e \u003cp\u003e15.2.1 Parkinson’s Disease 404\u003c\/p\u003e \u003cp\u003e15.2.2 Alzheimer’s Disease 404\u003c\/p\u003e \u003cp\u003e15.2.3 Alcohol Brain Damage 405\u003c\/p\u003e \u003cp\u003e15.2.4 Epilogue 405\u003c\/p\u003e \u003cp\u003eReferences 406\u003c\/p\u003e \u003cp\u003eIndex\u003c\/p\u003e","brand":"John Wiley \u0026 Sons Inc","offers":[{"title":"Default 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