Redox kinetics of the amyloid-β-Cu complex and its biological implications

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Title: Redox kinetics of the amyloid-β-Cu complex and its biological implications
Authors: Girvan, P
Teng, X
Brooks, N
Baldwin, G
Ying, L
Item Type: Journal Article
Abstract: The ability of the amyloid-β peptide to bind to redox active metals and act as a source of radical damage in Alzheimer’s disease has been largely accepted as contributing to the disease’s pathogenesis. However, a kinetic understanding of the molecular mechanism, which underpins this radical generation, has yet to be reported. Here we use a sensitive fluorescence approach, which reports on the oxidation state of the metal bound to the amyloid-β peptide and can therefore shed light on the redox kinetics. We confirm that the redox goes via a low populated, reactive intermediate and that the reaction proceeds via the Component I coordination environment rather than Component II. We also show that while the reduction step readily occurs (on the 10 ms time scale) it is the oxidation step that is rate-limiting for redox cycling.
Issue Date: 28-Sep-2018
Date of Acceptance: 28-Sep-2018
URI: http://hdl.handle.net/10044/1/64687
DOI: https://dx.doi.org/10.1021/acs.biochem.8b00133
ISSN: 1520-4995
Publisher: American Chemical Society
Start Page: 6228
End Page: 6233
Journal / Book Title: Biochemistry
Volume: 57
Issue: 43
Copyright Statement: © 2018 American Chemical Society. This is an open access article published under a Creative Commons Attribution (CC-BY) License, which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited.
Sponsor/Funder: British Heart Foundation
The Leverhulme Trust
Funder's Grant Number: PG/11/81/29130
RPG-2015-345
Keywords: Science & Technology
Life Sciences & Biomedicine
Biochemistry & Molecular Biology
ALZHEIMERS-DISEASE
A-BETA
A-BETA-16 PEPTIDE
OXIDATIVE STRESS
COPPER
BRAIN
MUTATIONS
CHEMISTRY
MECHANISM
INSIGHTS
0601 Biochemistry And Cell Biology
1101 Medical Biochemistry And Metabolomics
0304 Medicinal And Biomolecular Chemistry
Biochemistry & Molecular Biology
Publication Status: Published
Online Publication Date: 2018-09-28
Appears in Collections:Chemistry
Biological and Biophysical Chemistry
National Heart and Lung Institute
Faculty of Medicine
Faculty of Natural Sciences



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