The Catalytically Active Copper-Amyloid-Beta State: Coordination Site Responsible for Reactive Oxygen Species Production
Résumé
Amyloid plaques are a hallmark in the brain of Alzheimer’s disease (AD) victims. These plaques consist mainly of an aggregated peptide dubbed amyloid‐β (Aβ), which is also present in healthy brains in a soluble form. It is thought that soluble oligomeric forms of Aβ are the most toxic species, rather than more aggregated fibrils or protofibrils. The presence of oxidative damage on neuronal lipids and proteins is evidence of a link between oxidative stress and AD. Redox‐active copper ions are highly accumulated in amyloid plaques, where they bind to Aβ. Cu‐Aβ complexes are able to catalyze the production of reactive oxygen species (ROS), such as H2O2 and HO., in vitro. These reactions might contribute to the oxidative damage of diverse biomolecules observed in AD, including the peptide Aβ itself, which has been found to be oxidized in amyloid plaques in vivo.