Identification of key structural features of the elusive Cu-Aβ complex that generates ROS in Alzheimer's disease.

ABSTRACT: Oxidative stress is linked to the etiology of Alzheimer's disease (AD), the most common cause of dementia in the elderly. Redox active metal ions such as copper catalyze the production of Reactive Oxygen Species (ROS) when bound to the amyloid-β (Aβ) peptide encountered in AD. We propose that this reaction proceeds through a low-populated Cu-Aβ state, denoted the "catalytic in-between state" (CIBS), which is in equilibrium with the resting state (RS) of both Cu(i)-Aβ and Cu(ii)-Aβ. The nature of this CIBS is investigated in the present work. We report the use of complementary spectroscopic methods (X-ray absorption spectroscopy, EPR and NMR) to characterize the binding of Cu to a wide series of modified peptides in the RS. ROS production by the resulting Cu-peptide complexes was evaluated

SUBMITTER: Cheignon C 

PROVIDER: S-EPMC5613283 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature