Interactions of copper and copper chelate compounds with the amyloid beta peptide: An investigation into electrochemistry, reactive oxygen species and peptide aggregation.

Autor: Crnich E; Department of Biology, Lewis University, One University Pkwy, Romeoville, IL 60455, United States., Lullo R; Department of Biology, Lewis University, One University Pkwy, Romeoville, IL 60455, United States; Department of Chemistry, Lewis University, One University Pkwy, Romeoville, IL 60455, United States., Tabaka A; Department of Chemistry, Lewis University, One University Pkwy, Romeoville, IL 60455, United States., Havens MA; Department of Biology, Lewis University, One University Pkwy, Romeoville, IL 60455, United States., Kissel DS; Department of Chemistry, Lewis University, One University Pkwy, Romeoville, IL 60455, United States. Electronic address: kisselda@lewisu.edu.
Jazyk: angličtina
Zdroj: Journal of inorganic biochemistry [J Inorg Biochem] 2021 Sep; Vol. 222, pp. 111493. Date of Electronic Publication: 2021 May 29.
DOI: 10.1016/j.jinorgbio.2021.111493
Abstrakt: Alzheimer's disease is a fatal neurological disorder affecting millions of people worldwide with an increasing patient population as average life expectancy increases. Accumulation of amyloid beta (Aβ) plaques is characteristic of the disease and has been the target of numerous failed clinical trials. In light of this, therapeutics that target mechanisms of neuronal death beyond Aβ aggregation are needed. One potential target is the formation of reactive oxygen species (ROS) that are created during an interaction between Aβ and copper ions. This work shows that ROS production can be slowed by disrupting the interaction between Aβ and copper using copper chelating compounds. We demonstrated that ROS are produced in the presence of Aβ and copper in solution by monitoring H 2 O 2 production using a fluorescence-based assay, which increased when Cu 2+ interacted with Aβ. In addition, we were able to show reduced ROS production, without exacerbating the aggregation of Aβ and in some cases alleviating it, by adding copper chelating ligands to the solution. Using cyclic voltammetry, we investigated how these different ligands influenced the electrochemical behavior of copper in solution revealing important insights into the mechanisms of ROS production and chemical interactions that result in decreased ROS rates.
(Copyright © 2021 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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