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000145207 041__ $$aEnglish
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000145207 1001_ $$0P:(DE-2719)2630412$$aWolf, Hanna$$b0$$eFirst author$$udzne
000145207 1112_ $$aInternational Prion Congress—Prion 2015$$cAtlanta, GA$$d2015-05-26 - 2015-05-29$$wUSA
000145207 245__ $$aP.16: Glycosaminoglycan modulationaffects cellular prion replicationdownstream of PrPSc internalization
000145207 260__ $$c2015
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000145207 520__ $$aPrions are unconventional infectious agentscomposed primarily of misfolded aggregatedhost prion protein PrP, termed PrPSc. Conversion of cellular prion protein into PrPSc occurson the cell surface or along the endocytic pathway. The precise mechanisms and cellularrequirements for PrPSc uptake, the initial PrPScformation and the persistent PrPSc propagationstill remain unknown. Glycosaminoglycans(GAGs), highly-sulfated unbranched polysaccharides present on the cell surface and withinendocytic vesicles, have been implicated as firstattachment sites for prions and cofactors for replication. GAG mimetics and obstruction ofGAG sulfation affect prion replication, but sofar, comparative analysis of the role of GAGsduring the individual stages of infection by 22Lprion strain has not been performed. We examined the effect of the GAG mimetic, DS-500,and the sulfation inhibitor, NaClO3, on prioninfection by scrapie strain 22L in L929 cellsand organotypic cerebellar slices. Here weshow that both compounds change the cellulardistribution and levels of sulfated GAGs buthave divergent effects on cell surface and totalPrPC levels in L929 cells. Chemical manipulation of GAGs did not prevent PrPSc uptake,arguing against their role as essential attachment sites. Importantly, GAG undersulfationand DS-500 effectively antagonized de novoand chronic 22L prion infection in L929 cellsand organotypic cerebellar slices. We concludethat DS-500 and NaClO3 affect events downstream of the initial PrPSc attachment andinternalization.
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000145207 7001_ $$0P:(DE-2719)2811201$$aPleschka, Catharina$$b1$$udzne
000145207 7001_ $$0P:(DE-2719)2813235$$aGraßmann, Andrea$$b2$$udzne
000145207 7001_ $$0P:(DE-2719)2810581$$aHossinger, Andre$$b3$$udzne
000145207 7001_ $$0P:(DE-2719)2810422$$aMöhl, Christoph$$b4$$udzne
000145207 7001_ $$0P:(DE-2719)2651099$$aPaulsen, Lydia$$b5$$udzne
000145207 7001_ $$0P:(DE-2719)2481765$$aVorberg, Ina$$b6$$eLast author$$udzne
000145207 773__ $$0PERI:(DE-600)2267671-5$$nSuppelment 1$$pS19$$tPrion$$v9$$x1933-6896$$y2015
000145207 8564_ $$uhttps://www.tandfonline.com/doi/full/10.1080/19336896.2015.1033248
000145207 8564_ $$uhttps://pub.dzne.de/record/145207/files/DZNE-2020-00565_Restricted.pdf
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