CuII Binding to Various Forms of Amyloid-β Peptides: Are They Friends or Foes?

4 years ago

CuII Binding to Various Forms of Amyloid-β Peptides: Are They Friends or Foes?

Bruno Alies, Valentina Borghesani, Christelle Hureau

In the present microreview, we describe CuII binding to several forms of amyloid-β peptides, the peptides involved in Alzheimer's disease. It has indeed been shown that in addition to the “full-length” peptide that originates from the precursor protein after cleavage at the 1-position, several other shorter peptides do exist in large proportion and might be involved in the disease as well. CuII binding to amyloid-β peptides is one of the key interactions that impact both the aggregating properties of the amyloid peptides and the production of reactive oxygen species (ROS), two events that are linked to the etiology of the disease. Binding sites and affinity are described in correlation with CuII-induced ROS formation and CuII-altered aggregation for amyloid peptides starting at the 1-, 3-, 4-, and 11-positions, and for the corresponding pyroglutamate forms when they could be obtained (i.e., for peptides cleaved at the 3- and 11-positions). It appears that the current paradigm, which points to a toxic role of the CuII–amyloid-β interaction, might well be shifted towards a possible protective role when the peptides considered are the N-terminally truncated ones.CuII binding sites and affinity in the Cu(Aβ) complexes involved in Alzheimer's disease are described in combination with CuII-induced reactive oxygen species formation and Aβ-altered aggregation. This review highlights the paradigm shift from a toxic role of CuII/Aβ interaction to a possible protective one when Aβ is an N-terminal truncated peptide.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/ejic.201700776