ST1859 reduces prion infectivity and increase survival in experimental scrapie.

Abstract

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.

• Authors: Laura Colombo, Paola Piovesan, Orlando Ghirardi, Mario Salmona, Gianluigi Forloni
• Journal: Archives of virology (Arch Virol) Vol. 154 Issue 9 Pg. 1539-44 ( 2009) ISSN: 1432-8798 [Electronic] Austria
• PMID: 19685199 (Publication Type: Journal Article)

Chemical References

• 1,1-methylene-di-(2-naphthol)-3-acetyloxy-4-trimethylammonio-butanoate
• Naphthols
• PrP 27-30 Protein
• 1,1'-methylenedi-2-naphthol
• gamma-Aminobutyric Acid
• Endopeptidase K

Topics

• Animals
• Cricetinae
• Endopeptidase K (metabolism)
• Injections, Intraperitoneal
• Male
• Mesocricetus
• Naphthols (administration & dosage, chemistry, therapeutic use)
• PrP 27-30 Protein (antagonists & inhibitors, metabolism)
• Scrapie (drug therapy)
• gamma-Aminobutyric Acid (administration & dosage, analogs & derivatives, chemistry, therapeutic use)