Prion Diseases pp 277-283 | Cite as

Inhibition of formation of protease-resistant prion protein by Trypan Blue, Sirius Red and other Congo Red analogs

  • R. Demaimay
  • B. Chesebro
  • B. Caughey
Part of the Archives of Virology. Supplementa book series (ARCHIVES SUPPL, volume 16)


Five compounds related to Congo Red were found to inhibit generation of protease-resistant prion protein in a cell-free system. In this assay Trypan Blue, Evans Blue, Sirius Red F3B, Primuline and Thioflavin-S were all more inhibitory than Congo Red itself. In scrapie-infected mouse neuroblastoma cells one compound, Sirius Red F3B, was capable of blocking the formation of protease-resistant prion protein to a similar extent as Congo Red; however, the other four compounds were less effective. Some of these compounds should be considered for testing in TSE disease models in live animals.


Trypan Blue Prion Protein Prion Disease Bovine Spongiform Encephalopathy Evans Blue 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Caughey B, Chesebro B (1997) Prion protein and the transmissible spongiform encephalopathies. Trends Cell Biol 7: 56–62PubMedCrossRefGoogle Scholar
  2. 2.
    Caughey B, Race RE (1992) Potent inhibition of scrapie-associated PrP accumulation by Congo red. J Neurochem 59: 768–771PubMedCrossRefGoogle Scholar
  3. 3.
    Caughey B, Raymond GJ (1993) Sulfated polyanion inhibition of scrapie-associated PrP accumulation in cultured cells. J Virol 67: 643–650PubMedGoogle Scholar
  4. 4.
    Caughey WS, Raymond LD, Horiuchi M, Caughey B (1998) Inhibition of protease-resistant prion protein formation by porphyrins and phthalocyanines. Proc Natl Acad Sc i USA 95: 12117–12122CrossRefGoogle Scholar
  5. 5.
    Chesebro B (1999) Prion protein and the transmissible spongiform encephalopathy diseases. Neuron 24: 503–506PubMedCrossRefGoogle Scholar
  6. 6.
    Demaimay R, Adjou K, Lasmezas C, Lazarini F, Cherifi K, Seman M, Deslys JP, Dormont D (1994) Pharmacological studies of a new derivative of amphotericin B, MS-8209, in mouse and hamster scrapie. J Gen Virol 75: 2499–2503PubMedCrossRefGoogle Scholar
  7. 7.
    Demaimay R, Harper J, Gordon H, Weaver D, Chesebro B, Caughey B (1998) Structural aspects of Congo red as an inhibitor of protease-resistant prion protein formation. J Neurochem 71: 2534–2541PubMedCrossRefGoogle Scholar
  8. 8.
    Ehlers B, Diringer H (1984) Dextran sulphate 500 delays and prevents mouse scrapie by impairment of agent replication in spleen. J Gen Virol 65: 1325–1330PubMedCrossRefGoogle Scholar
  9. 9.
    Horiuchi M, Caughey B (1999) Prion protein interconversions and the transmissible spongiform encephalopathies. Structure Fold Des 7: R231–R240PubMedCrossRefGoogle Scholar
  10. 10.
    Ingrosso L, Ladogana A, Pocchiari M (1995) Congo red prolongs the incubation period in scrapie-infected hamsters. J Virol 69: 506–508PubMedGoogle Scholar
  11. 11.
    Kimberlin RH, Walker CA (1986) Suppression of scrapie infection in mice by heteropolyanion 23, dextran sulfate, and some other polyanions. Antimicrob Agents Chemother 3: 409–413CrossRefGoogle Scholar
  12. 12.
    Kocisko DA, Come JH, Priola SA, Chesebro B, Raymond GJ, Lansbury PT, Caughey B (1994) Cell-free formation of protease-resistant prion protein. Nature 370: 471–474PubMedCrossRefGoogle Scholar
  13. 13.
    Ladogana A, Casaccia P, Ingrosso L, Cibati M, Salvatore M, Xi YG, Masullo C, Pocchiari M (1992) Sulphate polyanions prolong the incubation period of scrapie-infected hamsters. J Gen Virol 73: 661–665PubMedCrossRefGoogle Scholar
  14. 14.
    Pocchiari M, Schmittinger S, Masullo C (1987) Amphotericin B delays the incubation period of scrapie in intracerebrally inoculated hamsters. J Gen Virol 68: 219–223PubMedCrossRefGoogle Scholar
  15. 15.
    Priola SA, Caughey B, Caughey WS (1999) Novel therapeutic uses for porphyrins and phthalocyanines in the transmissible spongiform encephalopathies. Curr Opin Microbiol 2: 563–566PubMedCrossRefGoogle Scholar
  16. 16.
    Race RE, Fadness LH, Chesebro B (1987) Characterization of scrapie infection in mouse neuroblastoma cells. J Gen Virol 68: 1391–1399PubMedCrossRefGoogle Scholar
  17. 17.
    Supattapone S, Nguyen HO, Cohen FE, Prusiner SB, Scott MR (1999) Elimination of prions by branched polyamines and implications for therapeutics. Proc Natl Acad Sci USA 96: 14529–14534PubMedCrossRefGoogle Scholar
  18. 18.
    Tagliavini F, McArthur RA, Canciani B, Giaccone G, Porro M, Bugiani M, Lievens PM, Bugiani O, Peri E, Dall’Ara P, Rocchi M, Poli G, Forloni G, Bandiera T, Varasi M, Suarato A, Cassutti P, Cervini MA, Lansen J, Salmona M, Post C (1997) Effectiveness of anthracycline against experimental prion disease in Syrian hamsters. Science 276: 1119–1122PubMedCrossRefGoogle Scholar
  19. 19.
    Weissmann C (1999) Molecular genetics of transmissible spongiform encephalo-pathies. J Biol Chem 274: 3–6PubMedCrossRefGoogle Scholar
  20. 20.
    Xi YG, Ingrosso L, Ladogana A, Masullo C, Pocchiari M (1992) Amphotericin B treatment dissociates in vivo replication of the scrapie agent from PrP accumulation. Nature 356: 598–60PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Wien 2000

Authors and Affiliations

  • R. Demaimay
    • 1
    • 2
  • B. Chesebro
    • 1
  • B. Caughey
    • 1
  1. 1.Laboratory of Persistent Viral DiseasesRML, NIAID, NIHHamiltonUSA
  2. 2.Laboratory of Secretory PathwaysImperial Cancer Research FundLondonUK

Personalised recommendations