Metal-Based Neurodegeneration - From Molecular Mechanisms to Therapeutic Strategies

Informationen zum Autor Robert Crichton and Roberta Ward, Unit of Biochemistry, Université Catholique de Louvain, Belgium Klappentext 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 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. Zusammenfassung 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. Inhaltsverzeichnis 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 Invol...

List of contents

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

Product details

• Authors: R Crichton, Rober Crichton, Robert Crichton, Robert (Universite Catholique De Louvain Crichton, Robert Ward Crichton, CRICHTON ROBERT WARD ROBERTA, Roberta Ward, Roberta (Universite Catholique de Louvain Ward, Ward Roberta
• Publisher: Wiley, John and Sons Ltd
• Languages: English
• Product format: Hardback
• Released: 08.11.2013
• EAN: 9781119977148
• ISBN: 978-1-119-97714-8
• No. of pages: 438
• Subjects: Natural sciences, medicine, IT, technology > Chemistry > Organic chemistry; Chemie, Neurologie, Medizin, Life Sciences, Neurology, Biowissenschaften, chemistry, Neurochemie, Neurochemistry, Medical Science