Prion diseases are fatal
neurodegenerative disorder associated with the conversion of the cellular
isoform of the
prion protein (PrP(C)) into the infectious
scrapie isoform (PrP(Sc)). Deposition of misfolded
prion proteins (PrP) on certain regions of brain can result in
prion diseases. As a membrane-bound chaperone of the endoplasmic reticulum (ER),
calnexin ensures the proper folding and quality control of newly synthesized
proteins. Using purified components in vitro,
calnexin associated with many
proteins and suppresses their thermal aggregation effectively. We for the first time analyzed PrP-
calnexin interaction. The immunoprecipitation, confocal microscope and native
polyacrylamide-gel electrophoresis results indicated that
calnexin could bind PrP both in vitro and in vivo. The turbidity result showed that
calnexin could supress thermal aggregation of PrP. MTT, flow cytometry (FCM) and
caspase activity studies demonstrated that
calnexin prevent caspase-3-mediated cytotoxicity induced by PrP. These results implied that
calnexin is potentially beneficial for the resistance of
prion diseases.