Document Detail


Elimination of prions by branched polyamines and implications for therapeutics.
MedLine Citation:
PMID:  10588739     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We report that branched polyamines, including polyamidoamide dendimers, polypropyleneimine, and polyethyleneimine, are able to purge PrP(Sc), the protease-resistant isoform of the prion protein, from scrapie-infected neuroblastoma (ScN2a) cells in culture. The removal of PrP(Sc) by 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 PrP(Sc) to 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 PrP(Sc) effectively from cells. The removal of PrP(Sc) by branched polyamines is attenuated by chloroquine in living cells, and exposure of scrapie-infected brain extracts with branched polyamines at acidic pH rendered the PrP(Sc) susceptible 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.
Authors:
S Supattapone; H O Nguyen; F E Cohen; S B Prusiner; M R Scott
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  96     ISSN:  0027-8424     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  1999 Dec 
Date Detail:
Created Date:  2000-01-05     Completed Date:  2000-01-05     Revised Date:  2013-06-11    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  14529-34     Citation Subset:  IM    
Affiliation:
Institute for Neurodegenerative Diseases, University of California, San Francisco, CA 94143-0518, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cells, Cultured
Dose-Response Relationship, Drug
Humans
Hydrogen-Ion Concentration
Mice
Neuroblastoma / drug therapy
Polyamines / therapeutic use*
Prions / metabolism*
Scrapie / drug therapy*
Structure-Activity Relationship
Time Factors
Grant Support
ID/Acronym/Agency:
AG02132/AG/NIA NIH HHS; AG08967/AG/NIA NIH HHS; NS14069/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Polyamines; 0/Prions
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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