Dual role of cellular prion protein in normal host and Alzheimer’s disease

Using PrP(C)-knockout cell lines, it has been shown that the inhibition of apoptosis through STI1 is mediated by PrP(C)-dependent SOD activation. Antioxidant PrP(C) may contribute to suppression of inflammasome activation. PrP(C) is functionally involved in copper metabolism, signal transduction, neuroprotection, and cell maturation. Recently several reports have shown that PrP(C) participates in trans-membrane signaling processes associated with hematopoietic stem cell replication and neuronal differentiation. In another role, PrP(C) also tends to function as a neurotoxic protein. Aβ oligomer, which is associated with neurodegeneration in Alzheimer’s disease (AD), has also been reported to act as a ligand of PrP(C). However, the physiological role of PrP(C) as an Aβ(42)-binding protein is not clear. Actually, PrP(C) is critical in Aβ(42)-mediated autophagy in neurons. PrP(C) shows a beneficial role in lipid rafts to promote autophagy. Further search for PrP(C)-interaction molecules using Prnp(−/−) mice and various types of Prnp(−/−) cell lines under various conditions may elucidate other important PrP(C) important functions.