The prion protein in neuroimmune crosstalk.

The cellular prion protein (PrP) is a medium-sized glycoprotein, attached to the cell surface by a glycosylphosphatidylinositol anchor. PrP is encoded by a single-copy gene, PRNP, which is abundantly expressed in the central nervous system and at lower levels in non-neuronal cells, including those of the immune system. Evidence from experimental knockout of PRNP in rodents, goats, and cattle and the occurrence of a nonsense mutation in goat that prevents synthesis of PrP, have shown that the molecule is non-essential for life. Indeed, no easily recognizable phenotypes are associate with a lack of PrP, except the potentially advantageous trait that animals without PrP cannot develop prion disease. This is because, in prion diseases, PrP converts to a pathogenic "scrapie" conformer, PrP, which aggregates and eventually induces neurodegeneration. In addition, endogenous neuronal PrP serves as a toxic receptor to mediate prion-induced neurotoxicity. Thus, PrP is an interesting target for treatment of prion diseases. Although loss of PrP has no discernable effect, alteration of its normal physiological function can have very harmful consequences. It is therefore important to understand cellular processes involving PrP, and research of this topic has advanced considerably in the past decade. Here, we summarize data that indicate the role of PrP in modulating immune signaling, with emphasis on neuroimmune crosstalk both under basal conditions and during inflammatory stress.