title: Lactoferrin induces cell surface retention of prion protein and inhibits prion accumulation.
abstract: 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.
authors: Prion Disease Research Center, National Institute of Animal Health, Ibaraki, Japan. gan@affrc.go.jp
authors: Yoshifumi
authors: Y
authors: Iwamaru
authors: Yoshihisa
authors: Y
authors: Shimizu
authors: Morikazu
authors: M
authors: Imamura
authors: Yuichi
authors: Y
authors: Murayama
authors: Ryo
authors: R
authors: Endo
authors: Yuichi
authors: Y
authors: Tagawa
authors: Yuko
authors: Y
authors: Ushiki-Kaku
authors: Takato
authors: T
authors: Takenouchi
authors: Hiroshi
authors: H
authors: Kitani
authors: Shirou
authors: S
authors: Mohri
authors: Takashi
authors: T
authors: Yokoyama
authors: Hiroyuki
authors: H
authors: Okada
mesh_terms: 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
chemical_list: D018621:PrPC Proteins; D018620:PrPSc Proteins; D007781:Lactoferrin