Impact of N‐Truncated Aβ Peptides on Cu‐ and Cu(Aβ)‐Generated ROS: Cu<sup>I</sup> Matters!
Charlène Esmieu, Guillaume Ferrand, Valentina Borghesani, Christelle Hureau
Abstract
Abstract In vitro Cu(Aβ 1– x )‐induced ROS production has been extensively 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 (H 2 N‐Xxx‐Zzz‐His) that confer them different coordination sites and higher affinities for Cu II compared to the Aβ 1– x 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 not been investigated to date. In contrast to Cu II , Cu I coordination is expected to be the same for N ‐truncated and N ‐intact peptides. Herein, we report in‐depth characterizations and ROS production studies of Cu (Cu I and Cu II ) 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 is present in the medium, albeit to a lesser extent than the unmodified counterpart. In addition, when used as competitor ligands (i.e., in the presence of Aβ 1–16 ), the N ‐truncated peptides are not able to fully preclude Cu(Aβ 1–16 )‐induced ROS production.