Inactivation of the Scrapie Agent by Ultraviolet Irradiation in the Presence of Chlorpromazine

Dees, Craig; Wade, William F.; German, Thomas L.; Marsh, Richard F.

doi:10.1099/0022-1317-66-4-845

Cited by 31 publications

(20 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recently, Korth and coworkers screened a variety of drugs already used for treatment of unrelated human disorders and known to penetrate the blood-brain barrier. They found that tricyclic derivatives of acridine and phenothiazine inhibit PrP Sc formation in scrapieinfected neuroblastoma cells (26), confirming earlier reports on antiprion activity of these compounds (27)(28)(29).…”

supporting

confidence: 73%

Tetracyclines affect prion infectivity

Forloni¹,

Iussich²,

Awan³

et al. 2002

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

178

102

View full text Add to dashboard Cite

Prion diseases are transmissible neurodegenerative disorders of humans and animals for which no effective treatment is available. Conformationally altered, protease-resistant forms of the prion protein (PrP) termed PrP Sc are critical for disease transmissibility and pathogenesis, thus representing a primary target for therapeutic strategies. Based on previous findings that tetracyclines revert abnormal physicochemical properties and abolish neurotoxicity of PrP peptides in vitro, we tested the ability of these compounds to interact with PrP Sc from patients with the new variant of Creutzfeldt-Jakob disease (vCJD) and cattle with bovine spongiform encephalopathy (BSE). The incubation with tetracycline hydrochloride or doxycycline hyclate at concentrations ranging from 10 M to 1 mM resulted in a dose-dependent decrease in protease resistance of PrP Sc . This finding prompted us to investigate whether tetracyclines affect prion infectivity by using an animal model of disease. Syrian hamsters were injected intracerebrally with 263K scrapie-infected brain homogenate that was coincubated with 1 mM tetracycline hydrochloride, 1 mM doxycycline hyclate, or vehicle solution before inoculation. Hamsters injected with tetracycline-treated inoculum showed a significant delay in the onset of clinical signs of disease and prolonged survival time. These effects were paralleled by a delay in the appearance of magnetic-resonance abnormalities in the thalamus, neuropathological changes, and PrP Sc accumulation. When tetracycline was preincubated with highly diluted scrapie-infected inoculum, one third of hamsters did not develop disease. Our data suggest that these well characterized antibiotics reduce prion infectivity through a direct interaction with PrP Sc and are potentially useful for inactivation of BSE-or vCJD-contaminated products and prevention strategies.

show abstract

supporting

confidence: 73%

Tetracyclines affect prion infectivity

Forloni¹,

Iussich²,

Awan³

et al. 2002

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

178

102

View full text Add to dashboard Cite

show abstract

“…Spongiform encephalopathies of man and animals are caused by unique transmissible agents that are unusually resistant to chemical inactivation and treatments that destroy or modify nucleic acid (Alper et al, 1967;Bellinger-Kawahara et al, 1987;Dees et al, 1985;Latarjet, 1979). In preparations enriched for infectivity, a predominant proteinase K-resistant form (PrP-res) of the endogenous prion protein (PrP) has been identified (Bolton et al, 1982;Diringer et al, 1983;Hope et al, 1986).…”

mentioning

confidence: 99%

Detection of proteinase K-resistant prion protein and infectivity in mouse spleen by 2 weeks after scrapie agent inoculation

Race

Ernst

1992

Journal of General Virology

View full text Add to dashboard Cite

“…Previous studies have shown that the scrapie agent is primarily associated with cell membrane (Millson et al, 197 l ;Semancik et al, 1976), and that treatment with organic solvents or high concentrations of ionic detergents reduces infectivity (Millson et al, 1976). These results suggest that the scrapie agent may require lipid-protein interactions for infectivity (Marsh et al, 1984a), and that membrane components may protect the scrapie agent from inactivation by treatments that damage nucleic acids (Latarjet, 1979;Kimberlin, 1982;Dees et al, 1985a). Recent studies have reported that a unique 26000 to 30000 mol.…”

Section: Introductionmentioning

confidence: 99%

Characterization of Proteins in Membrane Vesicles from Scrapie-infected Hamster Brain

Dees

German

Wade

et al. 1985

Journal of General Virology

Self Cite

View full text Add to dashboard Cite

SUMMARYPrevious studies have shown that the scrapie agent is highly membrane-associated. We examined the protein composition of gradient fractions enriched for large membrane vesicles prepared from scrapie-infected and uninfected hamster brain using various methods to extract membrane proteins. We also examined proteins in detergent-extracted membrane vesicles fractionated on CsCI gradients. No qualitative differences in protein composition were seen comparing scrapie-infected and uninfected samples by one-dimensional gel electrophoresis. Extraction of proteins from membrane vesicles by phenol, pyridine, perchloric acid or lithium diiodosalicylate also failed to reveal any unique proteins in scrapie-infected hamster brain. Attempts to solubilize hydrophobic proteins (proteolipids) from CsC1 gradient fractions into organic solvents were unsuccessful. These findings indicate that any hydrophobic protein associated with the scrapie agent is not a proteolipid, and that the ability of solvents to reduce scrapie infectivity is not a result of extraction of a proteolipid.

show abstract

Inactivation of the Scrapie Agent by Ultraviolet Irradiation in the Presence of Chlorpromazine

Cited by 31 publications

References 28 publications

Tetracyclines affect prion infectivity

Tetracyclines affect prion infectivity

Detection of proteinase K-resistant prion protein and infectivity in mouse spleen by 2 weeks after scrapie agent inoculation

Characterization of Proteins in Membrane Vesicles from Scrapie-infected Hamster Brain

Contact Info

Product

Resources

About