1st Edition

Brain Diseases and Metalloproteins

Edited By David R. Brown Copyright 2012
    438 Pages 23 Color & 43 B/W Illustrations
    by Jenny Stanford Publishing

    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.

    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

    Biography

    David R. Brown

    "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