Real-time evolution of Aβ40 metal-catalyzed oxidation reveals Asp1 as the main target and a dependence on metal binding site
Real-time evolution of Aβ40 metal-catalyzed oxidation reveals Asp1 as the main target and a dependence on metal binding site
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DOI：
10.1016/j.ica.2017.07.031
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发表时间：
2018-03-01
影响因子：
2.8
通讯作者：
Collin, Fabrice
中科院分区：
文献类型：
--
作者：
Cheignon, Clemence;Hureau, Christelle;Collin, Fabrice
Alzheimer's Disease (AD) is characterized by the deposition of amyloid plaques, mainly composed of aggregates of the Amyloid-beta peptide (A beta). There are evidences of oxidative damages on biomolecules and on A beta in vivo, suggesting a link between oxidative stress and AD. The dyshomeostasis of redox-active metal ions observed in AD and in particular the ability of Cu ions to catalyze reactive oxygen species (ROS) production when bound to A beta might contribute to the oxidative stress. In the present study, we have investigated by mass spectrometry (MS) the oxidative damages undergone by A beta(40) during the copper-catalyzed ROS production. N-terminal Asp1 was found to be the main target of ROS, along with His13 and His14, oxidized into oxo-histidine. As expected, the Met35 residue is also oxidized. The time evolution of A beta(40) oxidation indicates that the N-terminal part of the peptide, encompassing the main Cu binding sites, is the first target, the oxidation being stopped after several minutes. In contrast, the C-terminal one is regularly oxidized as a function of time although to a lesser extent. (C) 2017 Elsevier B.V. All rights reserved.
