Preface
Metals in Brain, Metal Transport, Storage and Homeostasis
Introduction - the importance of metal ions in brain function
Metal ion transport and storage - iron
Metal ion transport and storage - copper
Metal ion transport and storage - zinc
Metal ion transport and storage - other metals
Metals and their homeostasis (with particular reference to iron and copper)
References
Oxidative Stress and Redox-Active Metal Ions
Introduction - the oxygen paradox
Reactive oxygen species (ROS)
Reactive nitrogen species (RNS)
The targets of ROS and RNS
Cytoprotection against oxidative damage
Mitochondria, free radicals and signalling
Cyclin-dependent kinases
Apoptosis - programmed cell death
ROS, RNS and signal transduction
Molecules involved in the inflammatory pathway
References
Parkinson's Disease
Proteins involved in Parkinson's disease
Metal involvement in Parkinson's disease
Risk factors for Parkinson's disease
Mitochondrial dysfunction
Role of dopamine in Parkinson's disease
References
Alzheimer's Disease
Proteins involved in Alzheimer's disease
Metal involvement in Alzheimer's disease
Genetic and risk factors
Mitochondrial function in Alzheimer's disease
Oxidative stress
Role of acetyl choline in Alzheimer's disease
References
Huntington's Disease and Polyglutamine Expansion Neurodegenerative Diseases
Introduction - an overview of trinucleotide expansion diseases
PolyQ diseases
Structural models of polyQ protein aggregation
Mechanisms of cell death in polyQ diseases
Huntington's disease
Other polyQ disease proteins
References
Friedreich's Ataxia and Diseases Associated with Expansion of Non-Coding Triplets
Incidence and patholophysiology of Friedreich's ataxia
Molecular basis of the disease - triplet repeat expansions
Molecular basis of the disease - frataxin and its role in iron metabolism
Other diseases associated with expansion of non-coding triplets
References
Creutzfeldt-Jakob and Other Prion Diseases
Introduction
A brief history of prion diseases
The 'prion' of 'protein-only' hypothesis and conformation-based prion inheritance
Mechanisms of conformation-based prion transmission
Pathways of prion pathogenesis
Prion-metal interactions
References
Amyotrophic Lateral Sclerosis
Introduction
Major genes involved in ALS
Superoxide dismutase and ALS
Contributors to disease mechanisms in ALS
Other pathways that may cause damage to motor neurons
Conclusions
References
Other Neurological Diseases
Introduction
Aceruloplasminaemia
Wilson's and Menkes diseases
Hallervorden-Spatz syndrome
Neuroferritinopathy
Multiple sclerosis
HIV-associated dementia
References
Therapeutic Strategies to Combat the Onset and Progression of Neurodegenerative Diseases
Parkinson's disease
Alzheimer's disease
Huntington's disease and other polyQ disorders
Friedreich's ataxia and other diseases linked to non-coding triplet repeats
Prion diseases
Amyotrophic lateral sclerosis, ALS
Aceruloplasminaemia
Menkes disease
Wilson's disease
Multiple sclerosis
Future direction for therapeutic agents
References
Animal Models of the Various Neurodegenerative Diseases
Parkinson's disease animal models
Alzheimer's disease
Huntington's disease and polyQ
Friedreich's ataxia
Prion diseases
Amyotrophic lateral sclerosis, ALS
Aceruloplasminaemia
Menkes disease
Wilson's disease
Multiple sclerosis
References
Concluding Remarks
Therapeutic strategies
References
Index