Insoluble cellular prion protein and its association with prion and Alzheimer diseases

Prions: Beyond a Single Protein

“…Our previous study demonstrated that cell-expressed human wild-type PrP (PrP Wt ) or mutant PrP (PrP Mut ; including the naturally occurring mutation PrP T183A , PrP F198S , or PrP V180I ) contains iPrP C that is detectable with the 1E4 antibody; however, the 3F4-detected, PK-resistant PrP fragment is observed only in cells expressing PrP Mut (64,70 Using immunofluorescence microscopy, we observed that 1E4-detected PrP is localized mainly in the cytoplasm around the nucleus and is PK resistant (70,71) (Fig. 2).…”

“…Interestingly, using a combination of approaches, including ultracentrifugation and gel filtration (fast protein liquid chromatography), we consistently isolated not only iPrP C aggregates but also soluble PrP C oligomers from the healthy human brain (66). Therefore, similar to PrP Sc , PrP C may also possess chameleon-like conformations (71). The molecular function of iPrP C and its involvement in prion pathogenesis remain unknown.…”

New light on prions: putative role of co-operation of PrPc and Aβ proteins in cognition

“…PrP c is a glucolipid-anchored cell membrane sialoglycoprotein, which is localized in raft-like microdomains [57]. It is presented on the presynaptic and postsynaptic membranes [91] of neurons, of many brain areas including hippocampus and the cortex [73]. Membrane-anchored PrP c passes internalization and recycling through the endosomal pathway [58].…”

“…Due to the plenty of PrP c functions there are many possible molecular mechanisms in which this protein affects cognitive processes. PrP c is localized in the synaptic area, and it may interact with other proteins in this structure, playing a role in the synaptic plasticity [91]. An in vitro study has revealed that recombinant PrP (rPrP) induces rapid processing of both axons and dendrites as well as it increases the number of new synapses [40].…”

“…It has been proved that in uninfected human brains PrP is presented also in the form of oligomers, and even large aggregates, called insoluble PrP c (iPrP c ) which stand for ~5-25% of total PrP. It is proposed that if soluble PrP c can bind to soluble Aβ 42 , also iPrP c will bind insoluble Aβ, modulating its deposition [91]. It is therefore consistent with Takahashi et al's findings [82] (confirming the prior report of Ferrer et al [27]) indicating that PrP c is present in amyloid deposits.…”