title: Molecular interactions between prions as seeds and recombinant prion proteins as substrates resemble the biological interspecies barrier in vitro.
abstract: Prion diseases like Creutzfeldt-Jakob disease in humans, Scrapie in sheep or bovine spongiform encephalopathy are fatal neurodegenerative diseases, which can be of sporadic, genetic, or infectious origin. Prion diseases are transmissible between different species, however, with a variable species barrier. The key event of prion amplification is the conversion of the cellular isoform of the prion protein (PrP(C)) into the pathogenic isoform (PrP(Sc)). We developed a sodiumdodecylsulfate-based PrP conversion system that induces amyloid fibril formation from soluble α-helical structured recombinant PrP (recPrP). This approach was extended applying pre-purified PrP(Sc) as seeds which accelerate fibrillization of recPrP. In the present study we investigated the interspecies coherence of prion disease. Therefore we used PrP(Sc) from different species like Syrian hamster, cattle, mouse and sheep and seeded fibrillization of recPrP from the same or other species to mimic in vitro the natural species barrier. We could show that the in vitro system of seeded fibrillization is in accordance with what is known from the naturally occurring species barriers.
authors.affiliation: Institut für Physikalische Biologie, Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany.
authors.forename: Giannantonio
authors.initials: G
authors.lastname: Panza
authors.forename: Lars
authors.initials: L
authors.lastname: Luers
authors.forename: Jan
authors.initials: J
authors.lastname: Stöhr
authors.forename: Luitgard
authors.initials: L
authors.lastname: Nagel-Steger
authors.forename: Jürgen
authors.initials: J
authors.lastname: Weiss
authors.forename: Detlev
authors.initials: D
authors.lastname: Riesner
authors.forename: Dieter
authors.initials: D
authors.lastname: Willbold
authors.forename: Eva
authors.initials: E
authors.lastname: Birkmann
mesh_terms: D000682:Amyloid / Q000737:chemistry; D000818:Animals; D001921:Brain / Q000378:metabolism; D002417:Cattle; D002942:Circular Dichroism; D006224:Cricetinae; D066298:In Vitro Techniques; D007700:Kinetics; D008647:Mesocricetus; D051379:Mice; D019636:Neurodegenerative Diseases / Q000378:metabolism; D017096:Prion Diseases / Q000235:genetics* / Q000378:metabolism / Q000635:transmission*; D011328:Prions / Q000737:chemistry*; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins / Q000737:chemistry*; D012756:Sheep; D012967:Sodium Dodecyl Sulfate / Q000737:chemistry; D013045:Species Specificity; D014461:Ultracentrifugation
chemical_list: D000682:Amyloid; D011328:Prions; D011994:Recombinant Proteins; D012967:Sodium Dodecyl Sulfate