Lactoferrin induces cell surface retention of prion protein and inhibits prion accumulation.
Prion diseases are fatal neurodegenerative disorders, and the conformational conversion of normal cellular prion protein (PrP(C)) into its pathogenic, amyloidogenic isoform (PrP(Sc)) is the essential event in the pathogenesis of these diseases. Lactoferrin (LF) is a cationic iron-binding glycoprotein belonging to the transferrin (TF) family, which accumulates in the amyloid deposits in the brain in neurodegenerative disorders, such as Alzheimer's disease and Pick's disease. In the present study, we have examined the effects of LF on PrP(Sc) formation by using cell culture models. Bovine LF inhibited PrP(Sc) accumulation in scrapie-infected cells in a time- and dose-dependent manner, whereas TF was not inhibitory. Bioassays of LF-treated cells demonstrated prolonged incubation periods compared with non-treated cells indicating a reduction of prion infectivity. LF mediated the cell surface retention of PrP(C) by diminishing its internalization and was capable of interacting with PrP(C) in addition to PrP(Sc). Furthermore, LF partially inhibited the formation of protease-resistant PrP as determined by the protein misfolding cyclic amplification assay. Our results suggest that LF has multifunctional antiprion activities.
Iwamaru
Yoshifumi
Y
Prion Disease Research Center, National Institute of Animal Health, Ibaraki, Japan. gan@affrc.go.jp
Shimizu
Yoshihisa
Y
Imamura
Morikazu
M
Murayama
Yuichi
Y
Endo
Ryo
R
Tagawa
Yuichi
Y
Ushiki-Kaku
Yuko
Y
Takenouchi
Takato
T
Kitani
Hiroshi
H
Mohri
Shirou
S
Yokoyama
Takashi
T
Okada
Hiroyuki
H
D000818:Animals; D015153:Blotting, Western; D002417:Cattle; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism*; D002478:Cells, Cultured; D005434:Flow Cytometry; D007781:Lactoferrin / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D018621:PrPC Proteins / Q000378:metabolism*; D018620:PrPSc Proteins / Q000378:metabolism*; D012608:Scrapie / Q000378:metabolism
D018621:PrPC Proteins; D018620:PrPSc Proteins; D007781:Lactoferrin