Amyloid-beta and amyloid precursor protein metal complexes (Zn, Cu, Fe) (Aβ-APP-metal complexes)

Metal-bound amyloid-beta (Aβ) and amyloid precursor protein (APP) complexes are central to the "metal hypothesis" of Alzheimer's disease (Bush, 2003). APP and its proteolytic fragment, Aβ, contain specific binding sites for transition metals including zinc (Zn), copper (Cu), and iron (Fe) (Kepp, 2012). The binding of these metals to Aβ promotes its misfolding and aggregation into neurotoxic oligomers and insoluble plaques (Barnham & Bush, 2014). Furthermore, redox-active metals like Cu and Fe catalyze the production of hydrogen peroxide and other reactive oxygen species (ROS) via Fenton-like chemistry, leading to significant oxidative stress in the brain (Roberts et al., 2012). APP also functions as a ferroxidase that facilitates iron export; its dysfunction leads to toxic iron accumulation in neurons (Lei et al., 2012). Therapeutic interventions focus on metal-protein attenuating agents (MPAAs) that aim to normalize metal distribution and inhibit the formation of these toxic complexes (Ayton et al., 2015).

Other names

Metal-Aβ complexesMetal-APP complexesMetalloprotein complexes in Alzheimer'sZn-AβCu-AβFe-AβAβ-metal aggregates

Metal-protein attenuating agents (MPAAs) disrupt the interaction between transition metals and Aβ/APP to prevent aggregation and reduce oxidative stress.