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

Abstract

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 Aβ₄₂-binding protein is not clear. Actually, PrP^C is critical in Aβ₄₂-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.