Amyloid beta protein-induced zinc sequestration leads to synaptic loss via dysregulation of the ProSAP2/Shank3 scaffold

摘要

BackgroundMemory deficits in Alzheimer's disease (AD) manifest together with the loss of synapses caused by the disruption of the postsynaptic density (PSD), a network of scaffold proteins located in dendritic spines. However, the underlying molecular mechanisms remain elusive. Since it was shown that ProSAP2/Shank3 scaffold assembly within the PSD is Zn²⁺-dependent and that the amyloid beta protein (Aβ) is able to bind Zn²⁺, we hypothesize that sequestration of Zn²⁺ ions by Aβ contributes to ProSAP/Shank platform malformation.