Amphotericin B Inhibits the Generation of the Scrapie Isoform of the Prion Protein in Infected Cultures

Mangé, Alain; Nishida, Naoshi; Milhavet, Ollivier; McMahon, Hilary E.M.; Casanova, Danielle; Lehmann, Sylvain

doi:10.1128/jvi.74.7.3135-3140.2000

Cited by 106 publications

(68 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For instance, depletion of cholesterol, either by inhibiting its biosynthesis 51 or by addition of amphotericin B or filipin treatment (antibiotics known to sequester cholesterol), has been shown to decrease or inhibit PrP Sc formation. 52,53 On the other hand, when PrP C is recombinantly expressed as a transmembrane protein (CD4PrP C ), which is then targeted out of lipid rafts, PrP Sc formation is also abolished.…”

Section: The Gpi-anchor Of Prp C and Its Role In Prion Diseasementioning

confidence: 99%

The GPI-anchoring of PrP

Puig

Altmeppen

Glatzel

2014

Prion

View full text Add to dashboard Cite

Section: The Gpi-anchor Of Prp C and Its Role In Prion Diseasementioning

confidence: 99%

The GPI-anchoring of PrP

Puig

Altmeppen

Glatzel

2014

Prion

View full text Add to dashboard Cite

“…Chronically scrapie-infected cell lines have been extensively used as models for selecting 'anti-prion' drugs such as porphyrines , amphotericin B (Mange et al, 2000) and quinacrine (Doh-Ura et al, 2000). Since PrP-sen expression is essential for both TSE pathogenesis and conversion leading to PrP-res accumulation, we studied the effect of specific Prnp gene silencing molecules in scrapieinfected neuroblastoma cells (N2aS12sc + ).…”

mentioning

confidence: 99%

Specific inhibition of pathological prion protein accumulation by small interfering RNAs

Daude

Marella

Chabry

2003

Journal of Cell Science

View full text Add to dashboard Cite

Development of transmissible spongiform encephalopathies (TSEs)pathogenesis requires the presence of both the normal host prion protein(PrP-sen) and the abnormal pathological proteinase-K resistant isoform(PrP-res). PrP-res forms highly insoluble aggregates, with self-perpetuating properties, by binding and converting PrP-sen molecules into a likeness of themselves. In the present report, we show that small interfering RNA (siRNA)duplexes trigger specific Prnp gene silencing in scrapie-infected neuroblastoma cells. A non-passaged, scrapie-infected culture transfected with siRNA duplexes is depleted of PrP-sen and rapidly loses its PrP-res content. The use of different murine-adapted scrapie strains and host cells did not influence the siRNA-induced gene silencing efficiency. More than 80% of transfected cells were positive for the presence of fluorescein-labeled siRNA duplexes. No cytotoxicity associated with the use of siRNA was observed during the time course of these experiments. Despite a transient abrogation of PrP-res accumulation, our results suggest that the use of siRNA may provide a new and promising therapeutic approach against prion diseases.

show abstract

“…There was also no consistent assay of PrP-res in individual cells in the various laboratories (9). Nevertheless, while not practical for the high-yield production of infectious agent, these cultures were valuable in elucidating PrP metabolism, and removal of PrP after treatment with selected compounds (e.g., [10][11][12].…”

mentioning

confidence: 99%

Two Creutzfeldt–Jakob disease agents reproduce prion protein-independent identities in cell cultures

Arjona

Simarro

Islinger

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

125

View full text Add to dashboard Cite

Human Creutzfeldt-Jakob disease (CJD) and similar neurodegenerative diseases such as sheep scrapie are caused by a variety of related infectious agents. They are associated with abnormal host prion protein (PrP), which is assessed by limited proteolysis to yield resistant PrP bands (PrP-res). Although PrP-res has been posited as the infectious agent, purified PrP-res itself is not infectious. To establish the independence of CJD agent characteristics from those of PrP-res, two different mouse-passaged CJD strains were propagated in neuronal cell lines whose PrP-res patterns differ markedly from each other and from those found in infected brain. In mouse brain, the fast CJD strain, FU, elicits many PrP-res deposits, whereas the slow SY strain elicits few. Both strains evoked PrP-res in cultured murine cells, although SY induced PrP-res only transiently. PrP-res patterns in FU-and SY-infected GT1 cells were identical, and were significantly different from those in brain and in N2a cells. Nevertheless, all FU-infected cell lines reproduced their original fast disease in mice, even after extensive subculture, whereas SY-infected cells produced only slow disease. These data indicate PrP-res neither encodes nor alters agent-specific characteristics. PrP-res was also a poor predictor of infectivity because SY cells that had lost PrP-res were Ϸ10-fold more infectious than PrP-res-positive cultures. Furthermore, FU titers increased 650-fold, whereas PrP-res remained constant. Passaged FU-infected cells had titers comparable to brain, and >30% of cells displayed abundant cytoplasmic PrP-res aggregates that may trap agent. The continuous substantial replication of CJD in monotypic cells will further the discrimination of agent-specific molecules from pathological host responses to infection. transmissible encephalopathies ͉ agent strains ͉ in vitro propagation ͉ high infectivity ͉ in situ detection

show abstract

Amphotericin B Inhibits the Generation of the Scrapie Isoform of the Prion Protein in Infected Cultures

Cited by 106 publications

References 55 publications

The GPI-anchoring of PrP

The GPI-anchoring of PrP

Specific inhibition of pathological prion protein accumulation by small interfering RNAs

Two Creutzfeldt–Jakob disease agents reproduce prion protein-independent identities in cell cultures

Contact Info

Product

Resources

About