Intermediate redox states of Cu-Amyloid beta and Cu-alpha-synuclein complexes by variable temperature X-ray Absorption Spectroscopy

Several peptides and proteins related to neurodegenerative diseases such as amyloid-beta in Alzheimer’s or alpha-synuclein in Parkinson’s disease are intrinsically disordered proteins (IDP) and can bind Cu to form Cu-IDP complexes. These Cu-IDP are able to catalyse the production of reactive oxygen species (ROS) in the presence of a reducing agent (ascorbate) and dioxygen. This ROS production needs the redox cycling between the two redox states (Cu(I), Cu(II)) and is thought to contribute to the neurodegeneration. In the proposed project we propose to perform variable temperature XAS measurements in which we photoreduce Cu and then perform XAS experiments at different cryogenic temperatures in order to capture and characterize the intermediate redox states of Cu-Amyloid β and Cu-alpha-synuclein.