Rational Design of a Cu Chelator That Mitigates Cu-Induced ROS Production by Amyloid Beta.

ABSTRACT: Alzheimer's disease severely perturbs transition metal homeostasis in the brain leading to the accumulation of excess metals in extracellular and intraneuronal locations. The amyloid beta protein binds these transition metals, ultimately causing severe oxidative stress in the brain. Metal chelation therapy is an approach to sequester metals from amyloid beta and relieve the oxidative stress. Here we have designed a mixed N/O donor Cu chelator inspired by the proposed ligand set of Cu in amyloid beta. We demonstrate that the chelator effectively removes Cu from amyloid beta and suppresses reactive oxygen species (ROS) production by redox silencing and radical scavenging both in vitro and in cellulo. The impact of ROS on the extent of oxidation of the different aggregated forms of the peptid

SUBMITTER: Mitra S 

PROVIDER: S-EPMC9040527 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature