Metal-Based Neurodegeneration

From Molecular Mechanisms to Therapeutic Strategies

AvRobert Crichton,Roberta Ward

Inbunden, Engelska, 2013

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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 barrierImmune system and neuroinflammationAging and mild cognitive impairment, MCIParkinson’s DiseaseAlzheimer’s DiseaseCreutzfelt-Jakob and related prion diseasesAlcoholic Brain DamageTherapeutic strategies to combat the onset and progression of neurological diseasesThis 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.

Produktinformation

Utgivningsdatum:2013-11-08
Mått:180 x 254 x 26 mm
Vikt:1 007 g
Format:Inbunden
Språk:Engelska
Antal sidor:438
Upplaga:2
Förlag:John Wiley & Sons Inc
ISBN:9781119977148

Utforska kategorier

Kemi inom Naturvetenskap och teknik
Neurologi och klinisk neurofysiologi inom Medicin

Mer om författaren

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

Innehållsförteckning

Preface xi1 Brain Function, Physiology and the Blood–Brain Barrier 11.1 Introduction – An Overview of Brain Structure and Function 11.1.1 The Forebrain 11.1.2 The Midbrain 41.1.3 The Hindbrain 41.2 The Cell Types of the Brain 71.2.1 Neurons 71.2.2 Glial Cells 111.3 The Blood–Brain Barrier 19References 212 Role of Metal Ions in Brain Function, Metal Transport, Storage and Homoeostasis 232.1 Introduction – The Importance of Metal Ions in Brain Function 232.2 Sodium, Potassium and Calcium Channels and Pumps 242.3 Calcium and Signal Transduction 302.4 Zinc, Copper and Iron 372.5 Zinc 372.6 Copper 412.7 Iron 42References 483 Immune System and Neuroinflammation 513.1 General Introduction 513.1.1 Innate Immune Response and Neuroinflammation 513.1.2 Adaptive Immunity and Neuroinflammation 583.1.3 Adaptive Immunity and Neuroinflammation 593.1.4 Other Factors Contributing to Neuroinflammation 603.1.5 Anti-inflammatory Systems to Regulate Microglia Activation 603.2 Apoptosis 633.2.1 Iron Metabolic Regulators and Effectors during Inflammation 68References 724 Oxidative Stress in Neurodegenerative Diseases 754.1 Introduction – The Oxygen Paradox 754.2 Reactive Oxygen Species 764.3 Reactive Nitrogen Species 794.4 Cellular Defence Mechanisms against Oxidative Stress 824.5 ROS, RNS and Cellular Signalling 874.6 ROS, RNS and Oxidative Damage 914.7 Epigenetics 974.7.1 Histone Modifications 1004.8 Misfolded Protein Aggregates in Neurodegenerative Diseases 1014.9 The Amyloid State – Structure, Nucleation and Aggregation 102References 1075 Ageing and Mild Cognitive Impairment (MCI) 1115.1 Introduction 1115.1.1 Gene Involvement and Epigenetics 1125.1.2 DNA Methylation 1125.1.3 Histone Post-translational Modifications 1135.2 Prevalence of MCI 1145.2.1 MCI Presentation 1145.3 Brain Regions Involved 1155.3.1 Neurochemical Observations 1165.3.2 Factors Involved in the Ageing Process 1175.3.3 Mitochondria and the Ageing Process 1175.3.4 Free Radical Theory of Ageing 1185.3.5 Iron, Copper and Zinc in Ageing 1195.3.6 Risk Factors for Cognitive Decline 1215.3.7 APOe4 Isoforms and MCI 1225.3.8 Ageing and Immunity 1225.4 Proteostasis 1265.5 Conclusion 127References 1286 Parkinson’s Disease 1316.1 Risk Factors for PD 1316.2 Genetics of PD 1346.3 SNCA 1356.4 LRRK2 1356.5 Parkin 1356.6 DJ-1 1356.7 PINK1: PTEN-Induced Kinase 1366.8 Epigenetics 1366.9 miRNA 1366.10 Proteins Involved in PD 1376.11 Synucleins 1376.12 LRRK2 or PARK 8 1426.13 PINK1 or PTEN-Induced Putative Kinase 1, PARK6 1436.14 Parkin, PARK2 1446.15 Synphilin-1 1466.16 UCHL 1, Park 5 1476.17 DJ-1, PARK 7 1476.18 Metal Involvement in Parkinson’s Disease 1486.18.1 Iron 1486.18.2 Zinc 1536.18.3 Copper 1546.19 Neurotransmitters Involved in PD 1546.20 Mitochondrial Dysfunction 1566.21 PD and Inflammation 1566.22 Receptors Involved in the Inflammatory Response 1596.22.1 Toll-Like Receptors 1596.22.2 Glucocorticoid Receptor, GR 1596.22.3 CD200/CD200R 1606.22.4 Vitamin D Receptor (VDR) 1606.22.5 Peroxisome Proliferators-Activated Receptors 1616.23 Oxidative Stress and PD 161References 1637 Alzheimer’s Disease 1697.1 Introduction 1697.2 Epidemiology and Risk Factors for AD 1717.3 Genetics of AD 1737.3.1 Epigenetics 1747.4 Proteins Involved in Alzheimer’s Disease 1757.5 Metal Involvement in Alzheimer’s Disease 1797.6 Zinc Homoeostasis in AD 1817.7 Copper Homoeostasis in AD 1817.8 Iron Homoeostasis in AD 1837.9 Neurotransmitters Involved in AD 1857.9.1 Acetyl choline 1857.9.2 Glutamate 1877.10 Mitochondrial Function in Alzheimer’s Disease 1897.11 Neuroinflammation and AD 1917.12 Oxidative Stress 191References 1958 Huntington’s Disease and Polyglutamine Expansion Neurodegenerative Diseases 2038.1 Introduction 2038.2 An Overview of Trinucleotide Expansion Diseases 2048.3 Poly-Q Diseases 2048.4 Poly-Q Protein Aggregation and Poly-Q Disease Pathogenesis 2088.5 Huntington’s Disease 2118.6 Other Poly-Q Disease Proteins 2158.7 Spinocerebellar Ataxias 218References 2219 Friedreich’s Ataxia and Diseases Associated with Expansion of Non-Coding Triplets 2279.1 Incidence and Pathophysiology of Friedreich’s Ataxia 2279.2 Molecular Basis of the Disease: Triplet Repeat Expansions 2289.3 Molecular Basis of the Disease: Frataxin and Its Role in Iron Metabolism 2309.4 Other Diseases Associated with Expansion of Non-Coding Triplets 233References 23610 Creutzfeldt–Jakob and Other Prion Diseases 23910.1 Introduction 23910.2 A Brief History of Prion Diseases 24010.3 Structural Aspects of the Cellular Form of PrPC 24110.4 ‘Prion’ or ‘Protein-Only’ Hypothesis – Conformation-Based Prion Inheritance 24410.5 Models of PsPC to PsPSc Conversion 24610.6 Formation of Prion Aggregates 24810.7 Pathways of Prion Pathogenesis 253References 25611 Amyotrophic Lateral Sclerosis 26111.1 Introduction 26111.2 Major Genes Involved in ALS 26211.3 Superoxide Dismutase and ALS 26511.4 Contributors to Disease Mechanisms in ALS 26911.5 Excitotoxicity and Decreased Glutamate Uptake by Astroglia 26911.6 Endoplasmic Reticulum Stress 27011.7 Inhibition of the Proteasome 27011.8 Mitochondrial Damage 27111.9 Aberrant Secretion of Mutant SOD1 27111.10 Extracellular Superoxide Generation 27111.11 Axonal Disorganization and Disrupted Transport 27211.12 Microhaemorrhages of Spinal Capillaries 27211.13 Glial Cells in ALS 27311.14 ALS and Apoptosis 27311.15 Prion-Like Phenomena in ALS 27411.16 Conclusions 276References 27612 Alcoholic Brain Damage 28312.1 General Introduction 28312.2 Anatomy of Alcohol-Induced Damage 28512.3 Genetics of Alcohol-Induced Brain Damage 28612.3.1 Epigenetics 28612.3.2 MicroRNAs 28712.3.3 Genetics 28812.4 Factors Associated with Alcohol Brain Damage 29112.5 Factors Involved in Alcohol-Induced Brain Damage 29212.5.1 Neuropeptides 29212.5.2 Neurotransmitters 29312.5.3 Acetaldehyde 29412.5.4 Signalling Pathways 29512.5.5 Neuroinflammation and Alcohol 29612.5.6 Astrocytes and Alcohol 29712.5.7 Microglia and Alcohol 30012.5.8 NF-kB 30112.5.9 Toll-Like Receptors 30212.5.10 Oligodendrocytes and Alcohol 30312.5.11 Alcohol and Mitochondria 30312.5.12 Alcoholic Brain Damage and Oxidative Stress 304References 30513 Other Neurological Diseases 30913.1 Introduction 30913.2 Wilson’s and Menkes Diseases 30913.3 Neurodegeneration with Brain Iron Accumulation 31613.4 Aceruloplasminaemia 31613.5 Neuroferritinopathy 31813.6 Other Neurodegenerative Disorders with Brain Iron Accumulation 32013.7 Multiple Sclerosis 32313.8 HIV-Associated Neurocognitive Disorder 329References 33214 Therapeutic Strategies to Combat the Onset and Progression of Neurological Diseases 33714.1 Introduction 33714.2 Chelation of Excessive Metal Ions 33814.2.1 Chelation in Parkinson’s Disease 34114.2.2 Chelation Therapy in AD 34114.2.3 Chelation in Friedreich Ataxia 34314.3 Ageing and Cognitive Decline 34414.3.1 Saturated/Unsaturated Fat Intake 34414.3.2 Berries 34514.3.3 Creatine Supplementation 34614.3.4 Sirtuins 34714.3.5 Immunity 34714.3.6 Mitochondria Mutations 34814.4 Parkinson’s Disease 34814.4.1 Nutraceutical 34914.4.2 NASIs and COX2 Inhibitors 35114.4.3 Physical Exercise 35114.4.4 Dopamine Agonists 35214.4.5 Monoamine Oxidase Inhibitors 35414.4.6 L-DOPA 35514.4.7 Mitochondria and PD 35614.4.8 Sirtuins 35614.4.9 Creatine 35714.4.10 CoQ10 35814.4.11 Surgical Treatment for PD 35814.5 Alzheimer’s Disease 35914.5.1 Epigenetic Modifications 35914.5.2 Sirtuins 35914.5.3 Tau Kinase Inhibitors 35914.5.4 Neurotransmitters 36014.5.5 Anti-inflammatory Drugs 36014.5.6 Strategies to Remove Ab 36014.5.7 Ab Immunotherapy 36314.6 Huntington’s Disease and Other Poly-Q Diseases 36414.7 Friedreich’s Ataxia and Other Non-Coding Nucleotide Repeat Diseases 36714.8 Creutzfeld–Jakob and Other Prion Diseases 37014.9 Amyotrophic Lateral Sclerosis 37214.10 Alcohol Abuse 37314.11 Other Neurological Diseases 37814.11.1 Wilson’s and Menkes Diseases 37814.11.2 Neurodegeneration with Brain Iron Accumulation 37914.12 Multiple Sclerosis 38114.13 HIV-Associated Neurocognitive Disorder 386References 38715 Concluding Remarks 39515.1 New Innovative Therapeutics 40015.1.1 Stem Cells 40215.2 Biochemical Biomarkers of Neurodegenerative Diseases 40415.2.1 Parkinson’s Disease 40415.2.2 Alzheimer’s Disease 40415.2.3 Alcohol Brain Damage 40515.2.4 Epilogue 405References 406Index