Details

Autor(en) / Beteiligte

• Supattapone, Surachai
• Nguyen, Hoang-Oanh B.
• Cohen, Fred E.
• Prusiner, Stanley B.
• Scott, Michael R.

Titel

Elimination of Prions by Branched Polyamines and Implications for Therapeutics

Ist Teil von

• Proceedings of the National Academy of Sciences - PNAS, 1999-12, Vol.96 (25), p.14529-14534

Ort / Verlag

United States: National Academy of Sciences of the United States of America

Erscheinungsjahr

1999

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• We report that branched polyamines, including polyamidoamide dendimers, polypropyleneimine, and polyethyleneimine, are able to purge PrPSc, the protease-resistant isoform of the prion protein, from scrapie-infected neuroblastoma (ScN2a) cells in culture. The removal of PrPScby these compounds depends on both the concentration of branched polymer and the duration of exposure. Chronic exposure of ScN2a cells to low noncytotoxic concentrations of branched polyamines for 1 wk reduced PrPScto an undetectable level, a condition that persisted at least 3 wk after removal of the compound. Structure-activity analysis revealed that a high surface density of primary amino groups is required for polyamines to eliminate PrPSceffectively from cells. The removal of PrPScby branched polyamines is attenuated by chloroquine in living cells, and exposure of scrapie-infected brain extracts with branched polyamines at acidic pH rendered the PrPScsusceptible to protease in vitro, suggesting that endosomes or lysozomes may be the site of action. Our studies suggest that branched polyamines might be useful therapeutic agents for treatment of prion diseases and perhaps a variety of other degenerative disorders.