Interactions of recombinant prions with compounds of therapeutical significance

Biochemical and Biophysical Research Communications
Dessislava GeorgievaChristian Betzel

Abstract

The transformation of the cellular prion protein (PrP(C)) into the infectious form (PrP(Sc)) is implicated in the invariably fatal transmissible spongiform encephalopathies. To identify a mechanism to prevent the undesired PrP(C)-->PrP(Sc) transformation, we investigated the interactions of recombinant prion proteins with a number of potential therapeutic agents which inhibit the PrP(Sc) formation, infectivity, and the accumulation of the misfolded form. We show that the prion aggregates formed in the presence of six compounds have no beta-structure, which is typical of the infectious form, and possess considerably higher alpha-helical content than the normal PrP(C). The investigated compounds stimulate the formation of alpha-helices and the destruction of beta-structure. They prevent the transformation of alpha-helical structure into beta-sheets. Probably, this is the reason for the resistance to PrP(C)-->PrP(Sc) transformation in the presence of these compounds. The results may be useful for the future therapy of neurodegenerative diseases.

References

Apr 6, 1996·Lancet·R G WillP G Smith
Sep 18, 1997·Proceedings of the National Academy of Sciences of the United States of America·T L JamesF E Cohen
Oct 15, 1998·Proceedings of the National Academy of Sciences of the United States of America·P TremblayS B Prusiner
Dec 5, 1998·The Journal of Biological Chemistry·P C Pauly, D A Harris
Mar 3, 1999·Proceedings of the National Academy of Sciences of the United States of America·J H VilesH J Dyson
Jan 5, 2000·Proceedings of the National Academy of Sciences of the United States of America·R ZahnK Wüthrich
Jul 19, 2000·Proceedings of the National Academy of Sciences of the United States of America·F López GarciaK Wüthrich
Aug 16, 2001·Proceedings of the National Academy of Sciences of the United States of America·C KorthS B Prusiner
Jan 5, 2002·The Journal of Biological Chemistry·Holger LorenzHans A Kretzschmar
Aug 1, 2002·Proceedings of the National Academy of Sciences of the United States of America·Gianluigi ForloniFabrizio Tagliavini
Jul 15, 2003·Journal of Virology·A BarretJ P Deslys
Aug 9, 2003·Journal of Medicinal Chemistry·Martin VogtherrRalph Zahn
Nov 25, 2003·Journal of Veterinary Pharmacology and Therapeutics·T KosterE Gruys
Jan 15, 2004·Journal of Virology·Ikuko Murakami-KuboToru Iwaki
Jan 24, 2004·Dementia and Geriatric Cognitive Disorders·Masashi NakajimaYasufumi Kataoka
Sep 29, 2004·Biochemical and Biophysical Research Communications·Dessislava GeorgievaChristian Betzel
Oct 16, 2004·Journal of Medicinal Chemistry·Shane SellarajahIan H Gilbert

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Citations

Apr 25, 2013·Journal of Medicinal Chemistry·Tatiana StoilovaMario Salmona
Apr 9, 2014·Proceedings of the National Academy of Sciences of the United States of America·Jifeng BianGlenn C Telling
Apr 30, 2014·Pharmaceutical Development and Technology·Anne R KarowPatrick Garidel
Mar 10, 2018·Pathogens·Maria Letizia BarrecaEmiliano Biasini
Jan 1, 2007·Prion·Déborah TribouillardMarc Blondel

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