Prion protein lacks robust cytoprotective activity in cultured cells

Abstract

Background: The physiological function of the cellular prion protein (PrP C ) remains unknown. However, PrP C has been reported to possess a cytoprotective activity that prevents death of neurons and other cells after a toxic stimulus. To explore this effect further, we attempted to reproduce several of the assays in which a protective activity of PrP had been previously demonstrated in mammalian cells.

Expression of the Prion Protein Family Member Shadoo Causes Drug Hypersensitivity That Is Diminished by the Coexpression of the Wild Type Prion Protein

“…However, we were unable to detect a significant anti-apoptotic effect of PrP-WT expression under the condition of serum deprivation in Zpl2-1 cells. 3 These results are in line with a former report where no robust cytoprotective effect of PrP was found in the various models tested (45). Because Zpl2-1 cells repeatedly lost the expression of the transgenes during our work, thwarting progress, we used the SH-SY5Y cells for further studies.…”

Characterizing affinity epitopes between prion protein and β-amyloid using an epitope mapping immunoassay

“…12 Overall, PrPC may be involved in the neuroprotective and neurotoxic functions, but the effects remain unclear. 13 …”

Cytoprotective and toxic functions of the prion protein family

“…Although different cell types used in different studies may explain the observed differences our results are in line with a report where no robust cytoprotective effect of PrP was found in a similar cell culture model (96). While in our model WT PrP offered no protection, we found that the presence of PrPCR increased the sensitivity of the cells to serum deprivation.…”

“…Even though the expression of these mutants causes severe toxicity in PrP null transgenic mice (33)(34)(35) and in CGN cultures (64,97), they show reduced effect (43,98), or no effect (42,96) when expressed in immortalized cell lines. The most obvious phenotype associated with the Shmerling or CR mutations in PrP-s in cell models is the drug hypersensitivity and the occurrence of spontaneous inward cationic currents (37,39).…”