Comparison of protease-resistant prion protein inhibitors in cell cultures infected with two strains of mouse and sheep scrapie
| Autor: | Byron Caughey, David A. Kocisko, Lynne D. Raymond, Kevin M. Arnold, Abbi L. Engel, Emily A. Olsen, Didier Vilette, Kristin Harbuck |
|---|---|
| Přispěvatelé: | National Institutes of Health, Unité de recherche Virologie et Immunologie Moléculaires (VIM (UR 0892)), Institut National de la Recherche Agronomique (INRA) |
| Jazyk: | angličtina |
| Rok vydání: | 2005 |
| Předmět: |
PrPSc Proteins
Ratón animal diseases PRION Scrapie Biology Ferric Compounds Cell Line 03 medical and health sciences Mice 0302 clinical medicine Species Specificity In vivo medicine Animals Enzyme Inhibitors 030304 developmental biology chemistry.chemical_classification Pentosan Sulfuric Polyester 0303 health sciences Sheep General Neuroscience MOUSE SCRAPIE Epithelial Cells Pentosan polysulfate Virology In vitro 3. Good health nervous system diseases Enzyme chemistry Cell culture THERAPEUTICS [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] Rabbits SHEEP SCRAPIE INHIBITORS Cell culture assays Tannins 030217 neurology & neurosurgery medicine.drug Deuteroporphyrins |
| Zdroj: | Neuroscience Letters Neuroscience Letters, Elsevier, 2005, 388 (2), pp.106-111. ⟨10.1016/j.neulet.2005.06.053⟩ |
| ISSN: | 0304-3940 |
| DOI: | 10.1016/j.neulet.2005.06.053⟩ |
| Popis: | International audience; The transmissible spongiform encephalopathies (TSEs) are fatal neurodegenerative diseases. A primary therapeutic target for TSE intervention has been a protease-resistant form of prion protein known as PrPSc or PrP-res. In vitro testing of mouse scrapie-infected cell cultures has identified many PrP-res inhibitors that also have activity in vivo. Here we identify 32 new inhibitors of two strains of mouse scrapie PrP-res. Furthermore, to investigate the species-specificity of these and other PrP-res inhibitors, we have developed a high-throughput cell culture assay based on Rov9 cells chronically-infected with sheep scrapie. Of 32 inhibitors of murine PrP-res that were also tested in the Rov9 cells, only six showed inhibitory activity against sheep PrP-res. The three most potent inhibitors of both murine and ovine PrP-res formation (with 50% inhibition at ≤5_M) were tannic acid, pentosan polysulfate and Fe(III) deuteroporphyrin 2,4-bisethyleneglycol. The latter two have anti-mouse scrapie activity in vivo. These results identify new inhibitors of murine and ovine PrP-res formation and reinforce the idea that compounds effective against PrP-res from one species or strain cannot be assumed to be active against others. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect