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@ARTICLE{Lers:137547,
author = {Lüers, and Bannach, Oliver and Stöhr, Jan and Wördehoff,
Michael Marius and Wolff, Martin and Nagel-Steger, Luitgard
and Riesner, Detlev and Willbold, Dieter and Birkmann, Eva},
title = {{S}eeded {F}ibrillation as {M}olecular {B}asis of the
{S}pecies {B}arrier in {H}uman {P}rion {D}iseases},
journal = {PLoS one},
volume = {8},
number = {8},
issn = {1932-6203},
address = {Lawrence, Kan.},
publisher = {PLoS},
reportid = {FZJ-2013-03980},
pages = {e72623 -},
year = {2013},
abstract = {Prion diseases are transmissible spongiform
encephalopathies in humans and animals, including scrapie in
sheep, bovine spongiform encephalopathy (BSE) in cattle,
chronic wasting disease (CWD) in deer, and Creutzfeldt-Jakob
disease (CJD) in humans. The hallmark of prion diseases is
the conversion of the host-encoded prion protein (PrPC) to
its pathological isoform PrPSc, which is accompanied by PrP
fibrillation. Transmission is not restricted within one
species, but can also occur between species. In some cases a
species barrier can be observed that results in limited or
unsuccessful transmission. The mechanism behind interspecies
transmissibility or species barriers is not completely
understood. To analyse this process at a molecular level, we
previously established an in vitro fibrillation assay, in
which recombinant PrP (recPrP) as substrate can be
specifically seeded by PrPSc as seed. Seeding with purified
components, with no additional cellular components, is a
direct consequence of the “prion-protein-only”
hypothesis. We therefore hypothesise, that the species
barrier is based on the interaction of PrPC and PrPSc.
Whereas in our earlier studies, the interspecies
transmission in animal systems was analysed, the focus of
this study lies on the transmission from animals to humans.
We therefore combined seeds from species cattle, sheep and
deer (BSE, scrapie, CWD) with human recPrP. Homologous
seeding served as a control. Our results are consistent with
epidemiology, other in vitro aggregation studies, and
bioassays investigating the transmission between humans,
cattle, sheep, and deer. In contrast to CJD and BSE seeds,
which show a seeding activity we can demonstrate a species
barrier for seeds from scrapie and CWD in vitro. We could
show that the seeding activity and therewith the molecular
interaction of PrP as substrate and PrPSc as seed is
sufficient to explain the phenomenon of species barriers.
Therefore our data supports the hypothesis that CWD is not
transmissible to humans.},
cin = {ICS-6},
ddc = {500},
cid = {I:(DE-Juel1)ICS-6-20110106},
pnm = {452 - Structural Biology (POF2-452)},
pid = {G:(DE-HGF)POF2-452},
typ = {PUB:(DE-HGF)16},
UT = {WOS:000324527300092},
pubmed = {pmid:23977331},
doi = {10.1371/journal.pone.0072623},
url = {https://juser.fz-juelich.de/record/137547},
}