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Anti-Prion Screening for Acridine, Dextran, and Tannic Acid using Real Time–Quaking Induced Conversion: A Comparison with PrPSc-Infected Cell Screening.
- Source :
- PLoS ONE; 1/17/2017, Vol. 12 Issue 1, p1-13, 13p
- Publication Year :
- 2017
-
Abstract
- Prion propagation is mediated by the structural alteration of normal prion protein (PrP<superscript>C</superscript>) to generate pathogenic prion protein (PrP<superscript>Sc</superscript>). To date, compounds for the inhibition of prion propagation have mainly been screened using PrP<superscript>Sc</superscript>-infected cells. Real time–quaking-induced conversion (RT-QuIC) is one alternative screening method. In this study, we assessed the propagation inhibition effects of known anti-prion compounds using RT-QuIC and compared the results with those from a PrP<superscript>Sc</superscript>-infected cell assay. Compounds were applied to RT-QuIC reactions at 0 h or 22 h after prion propagation to determine whether they inhibited propagation or reduced amplified aggregates. RT-QuIC reactions in presence of acridine, dextran sulfate sodium (DSS), and tannic acid inhibited seeded aggregation with sporadic Creutzfeldt-Jakob disease at 0 h. After treatment at 22 h, amplified fluorescence was decreased in wells treated with either acridine or tannic acid. Compound activities were verified by western blot of RT-QuIC products and in a dye-independent conversion assay, the Multimer Detection System. Protease K-resistant PrP<superscript>Sc</superscript> fragments (PrP<superscript>res</superscript>) were reduced by DSS and tannic acid in the PrP<superscript>Sc</superscript>-infected cell assay. Importantly, these inhibitory effects were similar despite different treatment times (0 h versus 3 days). Consequentially, RT-QuIC enabled the more specific classification of compounds according to action (i.e., inhibition of prion propagation versus reduction of amplified aggregates). RT-QuIC addresses the limitations of cell-based screening methods and can be used to further aid our understanding of the mechanisms of action of anti-prion compounds. [ABSTRACT FROM AUTHOR]
- Subjects :
- PRIONS
TANNINS
CREUTZFELDT-Jakob disease
ACRIDINE
COMPARATIVE studies
Subjects
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 12
- Issue :
- 1
- Database :
- Complementary Index
- Journal :
- PLoS ONE
- Publication Type :
- Academic Journal
- Accession number :
- 120783345
- Full Text :
- https://doi.org/10.1371/journal.pone.0170266