In vitro Cu(Aβ1–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 (Aβ4–x and Aβ11–x) contain an amino-terminal copper and nickel (ATCUN) binding motif (H2N-Xxx-Zzz-His) that confer them different coordination sites and higher affinities for CuII compared to the Aβ1–x peptide. It has further been proposed that the role of Aβ4–x peptide is to quench CuII toxicity in the brain. However, the role of CuI coordination has not been investigated to date. In contrast to CuII, CuI 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 (CuI and CuII) complexes of the Aβ4–16 and Aβ11–16 N-truncated peptides. Our findings show that the N-truncated peptides do produce ROS when CuI 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 Aβ1–16), the N-truncated peptides are not able to fully preclude Cu(Aβ1–16)-induced ROS production.

Impact of N-Truncated Aβ Peptides on Cu- and Cu(Aβ)-Generated ROS: CuI Matters! / Esmieu, C.; Ferrand, G.; Borghesani, V.; Hureau, C.. - In: CHEMISTRY-A EUROPEAN JOURNAL. - ISSN 0947-6539. - 27:5(2021), pp. 1777-1786. [10.1002/chem.202003949]

Impact of N-Truncated Aβ Peptides on Cu- and Cu(Aβ)-Generated ROS: CuI Matters!

Borghesani V.;
2021-01-01

Abstract

In vitro Cu(Aβ1–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 (Aβ4–x and Aβ11–x) contain an amino-terminal copper and nickel (ATCUN) binding motif (H2N-Xxx-Zzz-His) that confer them different coordination sites and higher affinities for CuII compared to the Aβ1–x peptide. It has further been proposed that the role of Aβ4–x peptide is to quench CuII toxicity in the brain. However, the role of CuI coordination has not been investigated to date. In contrast to CuII, CuI 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 (CuI and CuII) complexes of the Aβ4–16 and Aβ11–16 N-truncated peptides. Our findings show that the N-truncated peptides do produce ROS when CuI 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 Aβ1–16), the N-truncated peptides are not able to fully preclude Cu(Aβ1–16)-induced ROS production.
2021
Impact of N-Truncated Aβ Peptides on Cu- and Cu(Aβ)-Generated ROS: CuI Matters! / Esmieu, C.; Ferrand, G.; Borghesani, V.; Hureau, C.. - In: CHEMISTRY-A EUROPEAN JOURNAL. - ISSN 0947-6539. - 27:5(2021), pp. 1777-1786. [10.1002/chem.202003949]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11381/2940591
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