Figure 1. PrPC antagonists improve synaptic function and spatial memory in a mouse model of Alzheimer’s disease.
Binding of amyloid-β oligomers (Aβo, black circles) to neuronal cellular prion protein (PrPC) leads to synaptic dysfunction and memory impairments. Centrally administered compound Z (red circles) and orally delivered Poly (4-styrenesulfonic acid-co-maleic acid) (PSCMA) that crosses the blood-brain barrier (BBB) (gray circles), both inhibit Aβo binding to PrPC on neurons (blue). This improves synaptic function and spatial memory deficit in Alzheimer’s mouse model of β-amyloidosis. Endothelial cells (red), astrocytes (purple) and oligodendrocytes (green) also express PrPC. Whether inhibiting PrPC-Aβo interactions on non-neuronal cell types can affect their function and/or contribute to the observed beneficial effects of compound Z or PSCMA, remains presently unclear. For example, whether compound Z or PSCMA can impact low-density lipoprotein receptor-related protein-1 (LRP1)-mediated clearance of PrPC-bound Aβ across the blood-brain barrier (BBB) is currently unknown. Do compound Z and PSCMA interact and alter functions of soluble PrPC interaction with Aβo which can affect fibril formation (gray box) remains elusive.