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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.
Autorentext
Robert Crichton and Roberta Ward,
Unit of Biochemistry, Université Catholique de Louvain,
Belgium
Zusammenfassung
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:
Inhalt
Preface xi
1 Brain Function, Physiology and the BloodBrain 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 BloodBrain 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 <p>...