Jump to main content
Jump to site search


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

Author affiliations

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 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.

Graphical abstract: Chemistry of mammalian metallothioneins and their interaction with amyloidogenic peptides and proteins

Back to tab navigation

Supplementary files

Publication details

The article was received on 16 Jun 2017 and first published on 08 Nov 2017


Article type: Tutorial Review
DOI: 10.1039/C7CS00448F
Citation: Chem. Soc. Rev., 2017, Advance Article
  •   Request permissions

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

    E. Atrián-Blasco, A. Santoro, D. L. Pountney, G. Meloni, C. Hureau and P. Faller, Chem. Soc. Rev., 2017, Advance Article , DOI: 10.1039/C7CS00448F

Search articles by author

Spotlight

Advertisements