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  • Chemistry of mammalian metallothioneins and their interaction with amyloidogenic peptides and proteins

    Author(s)
    Atrian-Blasco, Elena
    Santoro, Alice
    Pountney, Dean L
    Meloni, Gabriele
    Hureau, Christelle
    Faller, Peter
    Griffith University Author(s)
    Pountney, Dean L.
    Year published
    2017
    Metadata
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    Abstract
    Cu and Zn ions are essential in most living beings. Their metabolism is critical for health and mis-metabolism can be lethal. In the last two decades, a large body of evidence has reported the role of copper, zinc and iron, and oxidative stress in several neurodegenerative diseases like Alzheimer's, Parkinson's, prion diseases, etc. To what extent this mis-metabolism is causative or a consequence of these diseases is still a matter of research. In this context metallothioneins (MTs) appear to play a central gate-keeper role in controlling aberrant metal–protein interactions. MTs are small proteins that can bind high amounts ...
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    Cu and Zn ions are essential in most living beings. Their metabolism is critical for health and mis-metabolism can be lethal. In the last two decades, a large body of evidence has reported the role of copper, zinc and iron, and oxidative stress in several neurodegenerative diseases like Alzheimer's, Parkinson's, prion diseases, etc. To what extent this mis-metabolism is causative or a consequence of these diseases is still a matter of research. In this context metallothioneins (MTs) appear to play a central gate-keeper role in controlling aberrant metal–protein interactions. MTs are small proteins that can bind high amounts of Zn(II) and Cu(I) ions in metal-cluster arrangements via their cysteine thiolates. Moreover, MTs are well known antioxidants. The present tutorial outlines the chemistry underlying the interconnection between copper(I/II) and zinc(II) coordination to amyloidogenic proteins and MTs, and their redox properties in generation and/or silencing reactive oxygen species (overproduced in oxidative stress) and other reactants. These studies have revealed the coordination chemistry involved in neurodegenerative diseases and the interactions between MTs and amyloidogenic protein metal-complexes (like amyloid-β, α-synuclein and prion-protein). Overall, the protective role of MTs in neurodegenerative processes is emerging, serving as a foundation for exploring MT chemistry as inspiration for therapeutic approaches.
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    Journal Title
    Chemical Society Reviews
    Volume
    46
    Issue
    24
    DOI
    https://doi.org/10.1039/c7cs00448f
    Subject
    Chemical Sciences not elsewhere classified
    Chemical Sciences
    Publication URI
    http://hdl.handle.net/10072/372363
    Collection
    • Journal articles

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