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@INPROCEEDINGS{Wolf:145207,
author = {Wolf, Hanna and Pleschka, Catharina and Graßmann, Andrea
and Hossinger, Andre and Möhl, Christoph and Paulsen, Lydia
and Vorberg, Ina},
title = {{P}.16: {G}lycosaminoglycan modulationaffects cellular
prion replicationdownstream of {P}r{PS}c internalization},
journal = {Prion},
volume = {9},
number = {Suppelment 1},
issn = {1933-6896},
reportid = {DZNE-2020-00565},
pages = {S19},
year = {2015},
abstract = {Prions are unconventional infectious agentscomposed
primarily of misfolded aggregatedhost prion protein PrP,
termed PrPSc. Conversion of cellular prion protein into
PrPSc occurson the cell surface or along the endocytic
pathway. The precise mechanisms and cellularrequirements for
PrPSc uptake, the initial PrPScformation and the persistent
PrPSc propagationstill remain unknown.
Glycosaminoglycans(GAGs), highly-sulfated unbranched
polysaccharides present on the cell surface and
withinendocytic vesicles, have been implicated as
firstattachment sites for prions and cofactors for
replication. GAG mimetics and obstruction ofGAG sulfation
affect prion replication, but sofar, comparative analysis of
the role of GAGsduring the individual stages of infection by
22Lprion strain has not been performed. We examined the
effect of the GAG mimetic, DS-500,and the sulfation
inhibitor, NaClO3, on prioninfection by scrapie strain 22L
in L929 cellsand organotypic cerebellar slices. Here weshow
that both compounds change the cellulardistribution and
levels of sulfated GAGs buthave divergent effects on cell
surface and totalPrPC levels in L929 cells. Chemical
manipulation of GAGs did not prevent PrPSc uptake,arguing
against their role as essential attachment sites.
Importantly, GAG undersulfationand DS-500 effectively
antagonized de novoand chronic 22L prion infection in L929
cellsand organotypic cerebellar slices. We concludethat
DS-500 and NaClO3 affect events downstream of the initial
PrPSc attachment andinternalization.},
month = {May},
date = {2015-05-26},
organization = {International Prion Congress—Prion
2015, Atlanta, GA (USA), 26 May 2015 -
29 May 2015},
cin = {AG Vorberg / IDAF},
ddc = {570},
cid = {I:(DE-2719)1013004 / I:(DE-2719)1040200},
pnm = {342 - Disease Mechanisms and Model Systems (POF3-342)},
pid = {G:(DE-HGF)POF3-342},
experiment = {EXP:(DE-2719)IDAF-20190308},
typ = {PUB:(DE-HGF)1 / PUB:(DE-HGF)16},
url = {https://pub.dzne.de/record/145207},
}