A cellular gene encodes scrapie PrP 27-30 protein

Oesch, Bruno; Westaway, David; Wälchli, Monika; McKinley, Michael P.; Kent, Stephen B. H.; Aebersold, Ruedi; Barry, Ronald A.; Tempst, Paul; Teplow, David B.; Hood, Leroy; Prusiner, Stanley B.; Weissmann, Charles

doi:10.1016/0092-8674(85)90333-2

Cited by 1,428 publications

(946 citation statements)

References 61 publications

Supporting

Mentioning

878

Contrasting

Unclassified

Order By: Relevance

“…The notion that the infectious disease agent in TSE could be devoid of nucleic acids and primarily exists of protein, the so-called protein-only hypothesis, was first advanced in the 1960s based on experimental observations [1] and theory [2]. Prusiner and colleagues later showed that a particular protein was indeed required for infectivity [3][4][5]. Based on the name given to such a protein-based nucleic-acid free agent, a proteinaceous infectious particle or prion, the protein was called the prion protein (PrP).…”

Section: Introductionmentioning

confidence: 99%

Molecular Dynamics as an Approach to Study Prion Protein Misfolding and the Effect of Pathogenic Mutations

Kamp

Daggett

2011

Topics in Current Chemistry

View full text Add to dashboard Cite

Section: Introductionmentioning

confidence: 99%

Molecular Dynamics as an Approach to Study Prion Protein Misfolding and the Effect of Pathogenic Mutations

Kamp

Daggett

2011

Topics in Current Chemistry

View full text Add to dashboard Cite

“…Cardinal features of mammalian prion diseases are the accumulation of PK-resistant PrPSc in the brains of prion-infected individuals, concomitant with transmissible neurotoxicity [1,35]. We have previously shown that ovine PrP transgenic Drosophila accumulate disease-associated PrP after exposure to ovine prions [26].…”

Section: Prion Infectivity In Scrapie Brain-exposed Prp Transgenic Drmentioning

confidence: 99%

Bioassay of prion-infected blood plasma in PrP transgenic Drosophila

Thackray

Andréoletti

Bujdoso

2016

Biochemical Journal

View full text Add to dashboard Cite

In pursuit of a tractable bioassay to assess blood prion infectivity, we have generated prion protein (PrP) transgenic Drosophila, which show a neurotoxic phenotype in adulthood after exposure to exogenous prions at the larval stage. Here, we determined the sensitivity of ovine PrP transgenic Drosophila to ovine prion infectivity by exposure of these flies to a dilution series of scrapie-infected sheep brain homogenate. Ovine PrP transgenic Drosophila showed a significant neurotoxic response to dilutions of 10−2 to 10−10 of the original scrapie-infected sheep brain homogenate. Significantly, we determined that this prion-induced neurotoxic response in ovine PrP transgenic Drosophila was transmissible to ovine PrP transgenic mice, which is indicative of authentic mammalian prion detection by these flies. As a consequence, we considered that PrP transgenic Drosophila were sufficiently sensitive to exogenous mammalian prions to be capable of detecting prion infectivity in the blood of scrapie-infected sheep. To test this hypothesis, we exposed ovine PrP transgenic Drosophila to scrapie-infected plasma, a blood fraction notoriously difficult to assess by conventional prion bioassays. Notably, pre-clinical plasma from scrapie-infected sheep induced neurotoxicity in PrP transgenic Drosophila and this effect was more pronounced after exposure to samples collected at the clinical phase of disease. The neurotoxic phenotype in ovine PrP transgenic Drosophila induced by plasma from scrapie-infected sheep was transmissible since head homogenate from these flies caused neurotoxicity in recipient flies during fly-to-fly transmission. Our data show that PrP transgenic Drosophila can be used successfully to bioassay prion infectivity in blood from a prion-diseased mammalian host.

show abstract

“…Während PrP C durch die Proteinase K abgebaut werden kann, ist PrP Sc zum Teil Proteinase-resistent (Oesch et al 1985). Weiterhin ist PrP C, im Gegensatz zu der pathologischen Form, in nicht-denaturierenden Lösungsmitteln löslich (Meyer et al 1986).…”

Section: Im Prp Sc Ist Die Typische Tertiärstruktur Des Proteins Veräunclassified

“…(Prusiner 1982). Prionen besitzen keine nachweisbare Nukleinsäure, was sie von Viren, Bakterien, Pilzen und Protozoen abgrenzt (Oesch et al 1985). Prionen liegen nicht nur übertragbaren Erkrankungen zu Grunde, sie werden auch als Auslö-ser hereditärer und spontan entstehender Krankheiten gesehen (Prusiner 2001).…”

unclassified