PrP is another component of lipid rafts which was shown to act as a cellular receptor and change Ca 2+ signaling upon activation by some ligands, e.g., by antibody cross-linking in T-lymphocytes (Stuermer et al., 2005) . PrP c was also shown to be a receptor for Aβ oligomers at nanomolar concentrations and binding of Aβ oligomers to PrP c results in the blockage of hippocampal LTP. Incubation of hippocampal slices with PrP antibody abolishes the effect of Aβ oligomers and rescues synaptic plasticity (Lauren et al., 2009) . Most recently it was demonstrated PrP c also interacts with the NMDA receptor complex in a copper-dependent manner to allosterically reduce glycine affinity for the receptor and that Aβ(1-42), copper chelators or PrP c inactivation all enhance the activity of glycine at the receptor resulting in steady-state NMDAR currents and neurotoxicity. It was suggested that the physiological role of PrP c might be related to limitation of excessive NMDAR activity which might cause neuronal damage (You et al., 2012) . Together with the data on BACE1 regulation by PrP c this provides a unifying molecular mechanism explaining the interplay between toxic Aβ species, NMDA receptor-mediated toxicity and copper homeostasis in pathogenesis of AD (Rushworth and Hooper, 2011) .