Robert Crichton, Roberta Ward

Metal-Based Neurodegeneration

From Molecular Mechanisms to Therapeutic Strategies

• Gebundenes Buch

Produktbeschreibung

As life expectancy increases in the developed world, so does the incidence of neurodegenerative diseases of the human brain. Metal-Based Neurodegeneration provides a molecular biology perspective of many of the neurodegenerative diseases which currently plague humankind, including: * Alzheimer's Disease * Parkinson's Disease * Creutzfeldt-Jakob disease * Familial amyotrophic lateral sclerosis * Friedreich's ataxia * Multiple sclerosis * Wilson's disease * Hallervorden-Spatz syndrome * Huntington's disease In a dedicated chapter for each disease the characteristics of the disease are described along with the biochemical actors, including their normal, and pathological conformations. Emphasis is given on the role of metal-induced oxidative stress in the disease process, often resulting in the production of intracellular aggregates of the target proteins or peptides, including b-amyloid plaques and neurofibrillary tangles in Alzheimer's disease, Lewy bodies in Parkinson's disease, prion protein (PrP) plaques in prion diseases and nuclear inclusions in Huntington's. Finally the authors discuss the progress that is being made in understanding the pathogenesis of the diseases and the identification of targets for their treatment. Metal-Based Neurodegeneration is an essential survey of the molecular origin of neurodegenerative diseases for clinical and research scientists working in gerontology, neuropathology, metalloprotein mechanisms, and anyone with an interest in the diseases of ageing.

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Produktdetails

• Verlag: Wiley
• Seitenzahl: 240
• Erscheinungstermin: 1. Februar 2006
• Englisch
• Abmessung: 250mm x 174mm x 19mm
• Gewicht: 730g
• ISBN-13: 9780470022559
• ISBN-10: 0470022558
• Artikelnr.: 21265065

Autorenporträt

Professor Robert R. Crichton, Unité de Biochimie, Belgium. Professor Roberta J. Ward, Unité de Biochimie, Belgium.

Inhaltsangabe

Preface.
1 Metals in Brain, Metal Transport, Storage and Homeostasis.
1.1 Introduction - the importance of metal ions in brain function.
1.2 Metal ion transport and storage - iron.
1.3 Metal ion transport and storage - copper.
1.4 Metal ion transport and storage - zinc.
1.5 Metal ion transport and storage - other metals.
1.6 Metals and their homeostasis (with particular reference to iron and
copper).
References.
2 Oxidative Stress and Redox-Active Metal Ions.
2.1 Introduction - the oxygen paradox.
2.2 Reactive oxygen species (ROS).
2.3 Reactive nitrogen species (RNS).
2.4 The targets of ROS and RNS.
2.5 Cytoprotection against oxidative damage.
2.6 Mitochondria, free radicals and signalling.
2.7 Cyclin-dependent kinases.
2.8 Apoptosis - programmed cell death.
2.9 ROS, RNS and signal transduction.
2.10 Molecules involved in the inflammatory pathway.
References.
3 Parkinson's Disease.
3.1 Proteins involved in Parkinson's disease.
3.2 Metal involvement in Parkinson's disease.
3.3 Risk factors for Parkinson's disease.
3.4 Mitochondrial dysfunction.
3.5 Role of dopamine in Parkinson's disease.
References.
4 Alzheimer's Disease.
4.1 Proteins involved in Alzheimer's disease.
4.2 Metal involvement in Alzheimer's disease.
4.3 Genetic and risk factors.
4.4 Mitochondrial function in Alzheimer's disease.
4.5 Oxidative stress.
4.6 Role of acetyl choline in Alzheimer's disease.
References.
5 Huntington's Disease and Polyglutamine Expansion Neurodegenerative
Diseases.
5.1 Introduction - an overview of trinucleotide expansion diseases.
5.2 PolyQ diseases.
5.3 Structural models of polyQ protein aggregation.
5.4 Mechanisms of cell death in polyQ diseases.
5.5 Huntington's disease.
5.6 Other polyQ disease proteins.
References.
6 Friedreich's Ataxia and Diseases Associated with Expansion of Non-Coding
Triplets.
6.1 Incidence and patholophysiology of Friedreich's ataxia.
6.2 Molecular basis of the disease - triplet repeat expansions.
6.3 Molecular basis of the disease - frataxin and its role in iron
metabolism.
6.4 Other diseases associated with expansion of non-coding triplets.
References.
7 Creutzfeldt-Jakob and Other Prion Diseases.
7.1 Introduction.
7.2 A brief history of prion diseases.
7.3 The 'prion' of 'protein-only' hypothesis and conformation-based prion
inheritance.
7.4 Mechanisms of conformation-based prion transmission.
7.5 Pathways of prion pathogenesis.
7.6 Prion-metal interactions.
References.
8 Amyotrophic Lateral Sclerosis.
8.1 Introduction.
8.2 Major genes involved in ALS.
8.3 Superoxide dismutase and ALS.
8.4 Contributors to disease mechanisms in ALS.
8.5 Other pathways that may cause damage to motor neurons.
8.6 Conclusions.
References.
9 Other Neurological Diseases.
9.1 Introduction.
9.2 Aceruloplasminaemia.
9.3 Wilson's and Menkes diseases.
9.4 Hallervorden-Spatz syndrome.
9.5 Neuroferritinopathy.
9.6 Multiple sclerosis.
9.7 HIV-associated dementia.
References.
10 Therapeutic Strategies to Combat the Onset and Progression of
Neurodegenerative Diseases.
10.1 Parkinson's disease.
10.2 Alzheimer's disease.
10.3 Huntington's disease and other polyQ disorders.
10.4 Friedreich's ataxia and other diseases linked to non-coding triplet
repeats.
10.5 Prion diseases.
10.6 Amyotrophic lateral sclerosis, ALS.
10.7 Aceruloplasminaemia.
10.8 Menkes disease.
10.9 Wilson's disease.
10.10 Multiple sclerosis.
10.11 Future direction for therapeutic agents.
References.
11 Animal Models of the Various Neurodegenerative Diseases.
11.1 Parkinson's disease animal models.
11.2 Alzheimer's disease.
11.3 Huntington's disease and polyQ.
11.4 Friedreich's ataxia.
11.5 Prion diseases.
11.6 Amyotrophic lateral sclerosis, ALS.
11.7 Aceruloplasminaemia.
11.8 Menkes disease.
11.9 Wilson's disease.
11.10 Multiple sclerosis.
References.
12 Concluding Remarks.
12.1 Therapeutic strategies.
References.
Index.