ST1859 reduces prion infectivity and increase survival in experimental scrapie
| Autor: | Orlando Ghirardi, Laura Colombo, Mario Salmona, Paola Piovesan, Gianluigi Forloni |
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| Rok vydání: | 2009 |
| Předmět: |
Male
medicine.medical_specialty Period (gene) medicine.medical_treatment Scrapie Naphthols Medical microbiology Cricetinae Virology medicine Animals gamma-Aminobutyric Acid Infectivity Protease Mesocricetus biology General Medicine biology.organism_classification In vitro PrP 27-30 Protein Endopeptidase K Digestion Injections Intraperitoneal |
| Zdroj: | Archives of Virology. 154:1539-1544 |
| ISSN: | 1432-8798 0304-8608 |
| DOI: | 10.1007/s00705-009-0471-0 |
| Popis: | On the basis of the structural homologies between ST1859 (1[(2-hydroxy-1-naphtyl)methyl]-2-naphthol) and the anti-prion agents and its anti-amyloidogenic activity, we tested whether this molecule altered the biochemical properties of aggregates formed in vitro by synthetic prion peptides and affected prion infectivity in experimental scrapie. Co-incubation of ST1859 with the peptides PrP 106-126 and PrP 82-146 reduced their fibrillogenic capacity and their resistance to digestion with protease K. Hamsters inoculated with the ST1859-treated homogenate showed a significant delay in the onset of clinical signs of disease and longer survival. Survival was also significantly longer in infected hamsters treated peripherally with ST1859 for the whole post-inoculation period until the onset of clinical symptoms. Similar results were found with the analogue ST1745. Our data indicate that ST1859 reduces prion infectivity and can exert a therapeutic effect in experimental scrapie. |
| Databáze: | OpenAIRE |
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