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How Zn can impede Cu detoxification by chelating agents in Alzheimer's disease: a proof-of-concept study
The role of Cu and Zn ions in Alzheimer's disease is linked to the consequences of their coordination to the amyloid-β (Aβ) peptide, i.e. to the modulation of Aβ aggregation and to the production of Reactive Oxygen Species (ROS), two central events of the so-called amyloid cascade. The role of...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Royal Society of Chemistry
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5123634/ https://www.ncbi.nlm.nih.gov/pubmed/27711738 http://dx.doi.org/10.1039/c6dt02308h |
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author | Conte-Daban, Amandine Day, Adam Faller, Peter Hureau, Christelle |
author_facet | Conte-Daban, Amandine Day, Adam Faller, Peter Hureau, Christelle |
author_sort | Conte-Daban, Amandine |
collection | PubMed |
description | The role of Cu and Zn ions in Alzheimer's disease is linked to the consequences of their coordination to the amyloid-β (Aβ) peptide, i.e. to the modulation of Aβ aggregation and to the production of Reactive Oxygen Species (ROS), two central events of the so-called amyloid cascade. The role of both ions in Aβ aggregation is still controversial. Conversely the higher toxicity of the redox competent Cu ions (compared to the redox inert Zn ions) in ROS production is acknowledged. Thus the Cu ions can be considered as the main therapeutic target. Because Zn ions are present in higher quantity than Cu ions in the synaptic cleft, they can prevent detoxification of Cu by chelators unless they have an unusually high Cu over Zn selectivity. We describe a proof-of-concept study where the role of Zn on the metal swap reaction between two prototypical ligands and the Cu(Aβ) species has been investigated by several complementary spectroscopic techniques (UV-Vis, EPR and XANES). The first ligand has a higher Cu over Zn selectivity relative to the one of Aβ peptide while the second one exhibits a classical Cu over Zn selectivity. How Zn impacts the effect of the ligands on Cu-induced ROS production and Aβ aggregation is also reported. |
format | Online Article Text |
id | pubmed-5123634 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Royal Society of Chemistry |
record_format | MEDLINE/PubMed |
spelling | pubmed-51236342016-12-05 How Zn can impede Cu detoxification by chelating agents in Alzheimer's disease: a proof-of-concept study Conte-Daban, Amandine Day, Adam Faller, Peter Hureau, Christelle Dalton Trans Chemistry The role of Cu and Zn ions in Alzheimer's disease is linked to the consequences of their coordination to the amyloid-β (Aβ) peptide, i.e. to the modulation of Aβ aggregation and to the production of Reactive Oxygen Species (ROS), two central events of the so-called amyloid cascade. The role of both ions in Aβ aggregation is still controversial. Conversely the higher toxicity of the redox competent Cu ions (compared to the redox inert Zn ions) in ROS production is acknowledged. Thus the Cu ions can be considered as the main therapeutic target. Because Zn ions are present in higher quantity than Cu ions in the synaptic cleft, they can prevent detoxification of Cu by chelators unless they have an unusually high Cu over Zn selectivity. We describe a proof-of-concept study where the role of Zn on the metal swap reaction between two prototypical ligands and the Cu(Aβ) species has been investigated by several complementary spectroscopic techniques (UV-Vis, EPR and XANES). The first ligand has a higher Cu over Zn selectivity relative to the one of Aβ peptide while the second one exhibits a classical Cu over Zn selectivity. How Zn impacts the effect of the ligands on Cu-induced ROS production and Aβ aggregation is also reported. Royal Society of Chemistry 2016-10-21 2016-08-31 /pmc/articles/PMC5123634/ /pubmed/27711738 http://dx.doi.org/10.1039/c6dt02308h Text en This journal is © The Royal Society of Chemistry 2016 http://creativecommons.org/licenses/by-nc/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial 3.0 Unported License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Chemistry Conte-Daban, Amandine Day, Adam Faller, Peter Hureau, Christelle How Zn can impede Cu detoxification by chelating agents in Alzheimer's disease: a proof-of-concept study |
title | How Zn can impede Cu detoxification by chelating agents in Alzheimer's disease: a proof-of-concept study
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title_full | How Zn can impede Cu detoxification by chelating agents in Alzheimer's disease: a proof-of-concept study
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title_fullStr | How Zn can impede Cu detoxification by chelating agents in Alzheimer's disease: a proof-of-concept study
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title_full_unstemmed | How Zn can impede Cu detoxification by chelating agents in Alzheimer's disease: a proof-of-concept study
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title_short | How Zn can impede Cu detoxification by chelating agents in Alzheimer's disease: a proof-of-concept study
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title_sort | how zn can impede cu detoxification by chelating agents in alzheimer's disease: a proof-of-concept study |
topic | Chemistry |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5123634/ https://www.ncbi.nlm.nih.gov/pubmed/27711738 http://dx.doi.org/10.1039/c6dt02308h |
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