Prion diseases are fatal neurodegenerative disorders, and the conformational conversion of normal cellular prion protein (PrPC) into its pathogenic, amyloidogenic isoform (PrPSc) is the essential event in the pathogenesis of these diseases. Lactoferrin (LF) is a cationic iron-binding glycoprotein belonging to the transferrin family that 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 examined the effects of LF on PrPSc formation by using cell culture models. We demonstrated that LF can mediate the clearance of PrPSc and the reduction of prion infectivity in cells persistently infected with prion. The mechanism of action of LF potentially involves the cell-surface retention of PrP and/or binding to PrP. 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. Elucidation of the antiprion mechanisms of LF may contribute not only to the establishment of a new class of therapeutic agent but also to comprehension of the prion replication mechanisms.
(Research Team for Prion Diseases, TEL +81-29-838-7708)
Reference:
Iwamaru, Y., et al. (2008) J. Neurochem. 107: 636-646.
