N-truncated A β peptides impact on Cu and Cu(Aβ)-generated ROS: Cu(I) matters !

N-truncated Aβ peptides impact on Cu and Cu(Aβ)-generated ROS: Cu(I) matters ! Chemistry. 2020 Oct 15;: Authors: Esmieu C, Ferrand G, Borghesani V, Hureau C Abstract The in vitro Cu(Aβ 1-x ) induced ROS production has been extensively and thoroughly studied. Conversely, the ability of N-truncated isoforms of Aβ to alter the Cu-induced ROS production has been overlooked even though they are main constituents of amyloid plaques found in the human brain. N-truncated peptides at the positions 4 and 11 (Aβ 4-x and Aβ 11-x ) contain an amino-terminal copper and nickel (ATCUN) binding motif (NH 2 -Xxx-Zzz-His) that confer them different coordination sites and higher affinities for Cu(II) compared to the Aβ peptide. It has further been proposed that the role of Aβ 4-x peptide is to quench Cu(II) toxicity in the brain. However, the role of Cu(I) coordination has never been investigated so far. In contrast to Cu(II), the Cu(I) coordination is expected to be the same for N-truncated and N-intact peptides. Here, we report in-depth spectroscopic characterizations (Cu(II) and Cu(I)) complexes of the Aβ 4-16 and Aβ 11-16 N-truncated peptides and ROS production studies with copper (Cu(II) and Cu(I)) complexes of the Aβ 4-16 and Aβ 11-16 N-truncated peptides. Our findings show that the N-truncated peptides do produce ROS when Cu(I) in present in the medium, although to a lesser extent than the unmodified counterpart. In addition, when use...
Source: Chemistry - Category: Chemistry Authors: Tags: Chemistry Source Type: research