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| 001 | 140214 | ||
| 005 | 20240501120100.0 | ||
| 024 | 7 | _ | |a 10.1038/s41598-018-32581-1 |2 doi |
| 024 | 7 | _ | |a pmid:30242186 |2 pmid |
| 024 | 7 | _ | |a pmc:PMC6155003 |2 pmc |
| 024 | 7 | _ | |a altmetric:49943838 |2 altmetric |
| 037 | _ | _ | |a DZNE-2020-06536 |
| 041 | _ | _ | |a English |
| 082 | _ | _ | |a 600 |
| 100 | 1 | _ | |a Wüsten, Annick |0 P:(DE-2719)2810494 |b 0 |e First author |u dzne |
| 245 | _ | _ | |a A Bioluminescent Cell Assay to Quantify Prion Protein Dimerization. |
| 260 | _ | _ | |a [London] |c 2018 |b Macmillan Publishers Limited, part of Springer Nature |
| 264 | _ | 1 | |3 online |2 Crossref |b Springer Science and Business Media LLC |c 2018-09-21 |
| 264 | _ | 1 | |3 print |2 Crossref |b Springer Science and Business Media LLC |c 2018-12-01 |
| 336 | 7 | _ | |a article |2 DRIVER |
| 336 | 7 | _ | |a Output Types/Journal article |2 DataCite |
| 336 | 7 | _ | |a Journal Article |b journal |m journal |0 PUB:(DE-HGF)16 |s 1714481609_8224 |2 PUB:(DE-HGF) |
| 336 | 7 | _ | |a ARTICLE |2 BibTeX |
| 336 | 7 | _ | |a JOURNAL_ARTICLE |2 ORCID |
| 336 | 7 | _ | |a Journal Article |0 0 |2 EndNote |
| 520 | _ | _ | |a The prion protein (PrP) is a cell surface protein that in disease misfolds and becomes infectious causing Creutzfeldt-Jakob disease in humans, scrapie in sheep, and chronic wasting disease in deer and elk. Little is known regarding the dimerization of PrP and its role in disease. We developed a bioluminescent prion assay (BPA) to quantify PrP dimerization by bimolecular complementation of split Gaussia luciferase (GLuc) halves that are each fused to PrP. Fusion constructs between PrP and N- and C-terminal GLuc halves were expressed on the surface of RK13 cells (RK13-DC cells) and dimerized to yield a bioluminescent signal that was decreased in the presence of eight different antibodies to PrP. Dimerization of PrP was independent of divalent cations and was induced under stress. Challenge of RK13-DC cells with seven different prion strains did not lead to detectable infection but was measurable by bioluminescence. Finally, we used BPA to screen a compound library for compounds inhibiting PrP dimerization. One of the most potent compounds to inhibit PrP dimerization was JTC-801, which also inhibited prion replication in RML-infected ScN2a and SMB cells with an EC50 of 370 nM and 220 nM, respectively. We show here that BPA is a versatile tool to study prion biology and to identify anti-prion compounds. |
| 536 | _ | _ | |a 342 - Disease Mechanisms and Model Systems (POF3-342) |0 G:(DE-HGF)POF3-342 |c POF3-342 |f POF III |x 0 |
| 542 | _ | _ | |i 2018-09-21 |2 Crossref |u https://creativecommons.org/licenses/by/4.0 |
| 588 | _ | _ | |a Dataset connected to CrossRef, PubMed, |
| 650 | _ | 7 | |a Cations, Divalent |2 NLM Chemicals |
| 650 | _ | 7 | |a Prion Proteins |2 NLM Chemicals |
| 650 | _ | 2 | |a Animals |2 MeSH |
| 650 | _ | 2 | |a Biological Assay: methods |2 MeSH |
| 650 | _ | 2 | |a Cations, Divalent: metabolism |2 MeSH |
| 650 | _ | 2 | |a Cell Line |2 MeSH |
| 650 | _ | 2 | |a Cell Line, Tumor |2 MeSH |
| 650 | _ | 2 | |a Creutzfeldt-Jakob Syndrome: metabolism |2 MeSH |
| 650 | _ | 2 | |a Deer |2 MeSH |
| 650 | _ | 2 | |a Dimerization |2 MeSH |
| 650 | _ | 2 | |a Humans |2 MeSH |
| 650 | _ | 2 | |a Luminescent Measurements: methods |2 MeSH |
| 650 | _ | 2 | |a Mice |2 MeSH |
| 650 | _ | 2 | |a Prion Proteins: metabolism |2 MeSH |
| 650 | _ | 2 | |a Protein Folding |2 MeSH |
| 650 | _ | 2 | |a Rabbits |2 MeSH |
| 650 | _ | 2 | |a Scrapie: metabolism |2 MeSH |
| 650 | _ | 2 | |a Sheep |2 MeSH |
| 650 | _ | 2 | |a Wasting Disease, Chronic: metabolism |2 MeSH |
| 700 | 1 | _ | |a Pasham Parameshwar, Reddy |0 P:(DE-2719)2811529 |b 1 |u dzne |
| 700 | 1 | _ | |a Smiyakin, Andrej |0 P:(DE-2719)2811502 |b 2 |u dzne |
| 700 | 1 | _ | |a Bernis, Maria Eugenia |0 P:(DE-2719)2810557 |b 3 |u dzne |
| 700 | 1 | _ | |a Tamgüney, Gültekin |0 P:(DE-2719)2810376 |b 4 |e Last author |u dzne |
| 773 | 1 | 8 | |a 10.1038/s41598-018-32581-1 |b : Springer Science and Business Media LLC, 2018-09-21 |n 1 |p 14178 |3 journal-article |2 Crossref |t Scientific Reports |v 8 |y 2018 |x 2045-2322 |
| 773 | _ | _ | |a 10.1038/s41598-018-32581-1 |g Vol. 8, no. 1, p. 14178 |0 PERI:(DE-600)2615211-3 |n 1 |q 8:1<14178 |p 14178 |t Scientific reports |v 8 |y 2018 |x 2045-2322 |
| 856 | 4 | _ | |y OpenAccess |u https://pub.dzne.de/record/140214/files/DZNE-2020-06536.pdf |
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| 856 | 7 | _ | |2 Pubmed Central |u http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6155003 |
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| 920 | 1 | _ | |0 I:(DE-2719)1013022 |k AG Tamgüney 2 |l Prion and prion-like diseases |x 0 |
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