NR ANRZ
AU Meier,P.; Genoud,N.; Prinz,M.; Maissen,M.; Rülicke,T.; Zurbriggen,A.; Raeber,A.J.; Aguzzi,A.
TI Soluble Dimeric Prion Protein Binds PrPsc In Vivo and Antagonizes Prion Disease
QU Cell 2003 Apr 4; 113(1): 49-60
PT journal article
AB Conversion of cellular prion protein (PrPc) into a pathological conformer (PrPsc) is thought to be promoted by PrPsc in a poorly understood process. Here, we report that in wild-type mice, the expression of PrPc rendered soluble and dimeric by fusion to immunoglobulin Fcgamma (PrP-Fc(2)) delays PrPsc accumulation, agent replication, and onset of disease following inoculation with infective prions. In infected PrP-expressing brains, PrP-Fc(2) relocates to lipid rafts and associates with PrPsc without acquiring protease resistance, indicating that PrP-Fc(2) resists conversion. Accordingly, mice expressing PrP-Fc(2) but lacking endogenous PrPc are resistant to scrapie, do not accumulate PrP-Fc(2)(Sc), and do not transmit disease to others. These results indicate that various PrP isoforms engage in a complex in vivo, whose distortion by PrP-Fc(2) affects prion propagation and scrapie pathogenesis. The unique properties of PrP-Fc(2) suggest that soluble PrP derivatives may represent a new class of prion replication antagonists.
AD Institute of Neuropathology, Schmelzbergstrasse, University Hospital of Zürich, Zürich, Switzerland
SP englisch
PO USA