Copper and zinc ions associated with Amyloid-beta (Cu/Zn-Aβ)

Copper and zinc ions associated with Amyloid-beta (Aβ) are critical pathological targets in Alzheimer's disease, where they facilitate the aggregation and neurotoxicity of Aβ peptides (Bush, 2003, Nature Reviews Neuroscience). Zinc ions (Zn2+) bind to the N-terminal histidine residues of Aβ, promoting the formation of stable, protease-resistant oligomers and plaques (Fallon et al., 2021, Chemical Science). Copper ions (Cu2+) also bind to Aβ, forming a redox-active complex that catalyzes the production of reactive oxygen species (ROS), leading to significant oxidative stress and neuronal damage (Barnham & Bush, 2014, Chemical Society Reviews). Therapeutic intervention focuses on Metal-Protein Attenuating Agents (MPAAs) like PBT2, which are designed to cross the blood-brain barrier, disrupt the Aβ-metal bond, and redistribute the sequestered ions back into the intracellular compartment to restore normal synaptic function (Adlard et al., 2008, Neuron). This dual action aims to reduce the amyloid burden while mitigating the cognitive deficits associated with metal dyshomeostasis in the aging brain.

Other names

Metal-associated Amyloid-betaCu-Aβ and Zn-Aβ complexesAmyloid-beta-metal ion complexAβ-metal adducts

Metal-protein attenuation and ion redistribution: drugs disrupt the coordination of Cu2+ and Zn2+ to Aβ, promoting plaque dissolution and reducing ROS production while restoring intracellular metal levels (Adlard et al., 2008, Neuron).