184865-04-1Relevant articles and documents
Real-time evolution of Aβ40 metal-catalyzed oxidation reveals Asp1 as the main target and a dependence on metal binding site
Cheignon, Clémence,Hureau, Christelle,Collin, Fabrice
, p. 111 - 118 (2017/10/05)
Alzheimer's Disease (AD) is characterized by the deposition of amyloid plaques, mainly composed of aggregates of the Amyloid-β peptide (Aβ). There are evidences of oxidative damages on biomolecules and on Aβ 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 Aβ might contribute to the oxidative stress. In the present study, we have investigated by mass spectrometry (MS) the oxidative damages undergone by Aβ40 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 Aβ40 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.
