Brain Diseases and Metalloproteins

Brain Diseases and Metalloproteins

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Features

  • Presents the most up-to-date research in context with the background of the disease
  • Addresses basic researchers in the lab as well as specialist clinicians who want to keep up with the latest research discussed in an authoritative manner

Summary

This book describes the latest research on neurodegenerative disease and metal-binding proteins. It lays strong emphasis on biochemistry and cell biology. The diseases covered in the book include Parkinson’s disease, Alzheimer’s disease, prion disease, and ALS. The chapters separately examine such issues as mechanisms of metal binding, metal-induced structural changes in proteins, alterations in cellular metal metabolism in disease, and attempts at a therapeutic approach based on protein metal binding.

Table of Contents

Introduction David R. Brown
Brain Diseases
Metalloproteins
A Possible Key Role for Redox-Active Metal Ions and Soluble Oligomers in Neurodegenerative Disease Brian J. Tabner, Susan Moore, Jennifer Mayes, and David Allsop
Summary
Introduction to the Proteopathies
Mutations in Genes Associated with Protein Processing and Aggregation Cause Inherited Forms of Proteopathy
The Toxic Eff ects of Protein Oligomers
The Generation of Hydrogen Peroxide by Aβ Other Aggregating Protein Systems Mechanism of Hydrogen Peroxide Formation and Aβ Oxidation Concluding Comments Modelling of the Metal Binding Sites in Proteins Involved in Neurodegeneration Ewa Gralka, Daniela Valensin, Maurizio Remelli, and Henryk Kozlowski
Introduction
Peptides as Models for Unstructured Protein Interactions with Metal Ions
Structural Approach to Metal-Peptide Interactions (Role of His as the Metal Ion Binding Site)
Thermodynamic and Speciation Studies
Impact of Metal Ions on Prion Protein Fibril Formation
Impact of Metal-Peptide Interaction on Oxidative Stress
Mammalian Metallothioneins Duncan E. K. Sutherland and Martin J. Stillman
Metallothionein
Techniques for Studying Metallothioneins
MT-1 and MT-2: Inducible Metallothioneins
MT-3: A Central Nervous System Metallothionein
Copper Transporting P-Type ATPases in the Brain Sharon La Fontaine, James Camakaris, and Julian Mercer
ATP7A in the Brain
ATP7B in the Brain
Conclusion
Role of the Amyloid Precursor Protein and Copper in Alzheimer’s Disease Loredana Spoerri, Kevin J. Barnham, Gerd Multhaup and Roberto Cappai
The Amyloid Precursor Protein
Copper Physiology
Copper and Alzheimer’s Disease
APP, Copper and Alzheimer’s Disease
APP Copper Binding Domain (CuBD)
Conclusions
Role of Aluminum and Other Metal Ions in the Pathogenesis of Alzheimer’s Disease Silvia Bolognin and Paolo Zatta
Alzheimer’s Disease The Amyloid Cascade and Oligomer Hypothesis Metal Dysmetabolism in AD The Role of Metal Ions in the Aggregation and Toxicity of Aβ Aβ and Cell Membranes Amyloid Metal Complexes and Ca Conclusion
Prion Diseases, Metals and Antioxidants Paul Davies and David R. Brown
The Transmissible Spongiform Encephalopathies
The Prion Protein
PrP and Copper Binding
The Implications of Copper Binding
Other Metals
Metals and Aggregation
Changes in Brain Metals
PrP Survival in the Environment
Conclusion
Emerging Role for Copper-Bound α-Synuclein in Parkinson’s Disease Etiology Heather R. Lucas and Jennifer C. Lee
Introduction
Interaction of Copper(II) and α-Synuclein Metal-Catalysed Protein Oxidation Conclusion
Interactions of α-Synuclein with Metal Ions: New Insights into the Structural Biology and Bioinorganic Chemistry of Parkinson’s Disease Andrés Binolfi and Claudio O. Fernández
Introduction
Interaction of AS with Cu(II) Ions
Interaction of AS with Other Divalent Metal Ions
Structural Details Behind the Specificity of AS-Cu(II) Interactions
Conclusions and Future Perspectives
An Attempt to Treat Amyotrophic Lateral Sclerosis by Intracellular Copper Modification Using Ammonium Tetrathiomolybdate and/or Metallothionein: Fundamentals and Perspective 367 Shin-Ichi Ono, Ei-Ichi Tokuda, Eriko Okawa, and Shunsuke Watanabe
Introduction
Causes of ALS
Characterization of G93A Mutant SOD1 Mouse
Metallothionein, Copper Ions and ALS
Cellular Damage by Copper Overload
Therapeutic Strategy in Mutant SOD1 Mice Based on "Intracellular Cu Dysregulation" Hypothesis: Intracellular Copper Removal Using Ammonium Tetrathiomolybdate
Therapeutic Strategy in Mutant SOD1 Mice Based on "Intracellular Cu Dysregulation" Hypothesis: Intracellular Copper Modification Using a Metallothionein-I Isoform
Conclusion
Index

Editorial Reviews

"This is an authoritative and thorough overview of a field of growing significance to neuroscience. Metal ion metabolism is intimately involved with the causes of most neurodegenerative disease, and is an area of unexploited importance for potential drug development. This work is timely, and tremendously useful with an excellent choice of subjects, beautifully and rigorously presented"
—Prof. Ashley I. Bush - University of Melbourne, Australia