HOMEPRODUCTSSERVICESCOMPANYCONTACTFAQResearchDictionaryPharmaMobileSign Up FREE or Login

Cationic lipopolyamines induce degradation of PrPSc in scrapie-infected mouse neuroblastoma cells.

Abstract
In prion diseases the endogenous prion protein (PrPC) is converted into an abnormally folded isoform, denoted PrPSc, which represents the major component of infectious scrapie prions. The mechanism of the conversion is largely unknown, but the conversion is thought to occur after PrPC has reached the plasma membrane. Here we show that exogenous administration of the cationic lipopolyamine DOSPA interfered with the accumulation of PrPSc in scrapie-infected neuroblastoma cells. Structural analysis of the compounds tested revealed that inhibition of PrPSc was specific for lipids with a headgroup composed of the polyamine spermine and a quarternary ammonium ion between the headgroup and the lipophilic tail. The cationic lipopolyamine DOSPA induced the cellular degradation of preexisting PrPSc aggregates within 12 hours and interfered with the de novo synthesis of PrPSc. Biosynthesis of PrPC, or the assembly of sphingolipid-cholesterol microdomains (rafts) on the plasma membrane, were not affected by this inhibitor. After removal of DOSPA and replating into normal medium propagation of PrPSc commenced, although initially at a reduced rate. Incubation of ScN2a cells in free spermidine had no inhibitory effect on the accumulation of PrPSc. Our results indicate that membrane targeting of a small polyamine molecule creates a potent inhibitor of PrPSc propagation and offers the possibility to degrade preexisting PrPSc aggregates in living cells.
AuthorsK F Winklhofer, J Tatzelt
JournalBiological chemistry (Biol Chem) 2000 May-Jun Vol. 381 Issue 5-6 Pg. 463-9 ISSN: 1431-6730 [Print] GERMANY
PMID10937879 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Cations
  • Polyamines
  • PrPSc Proteins
Topics
  • Animals
  • Cations
  • Hydrolysis
  • Mice
  • Neuroblastoma (virology)
  • Polyamines (metabolism)
  • PrPSc Proteins (metabolism)
  • Tumor Cells, Cultured

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research network!


Choose Username:
Email:
Password:
Verify Password: