| Elimination of prions by branched polyamines and implications for therapeutics. | |
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MedLine Citation:
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PMID: 10588739 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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S Supattapone; H O Nguyen; F E Cohen; S B Prusiner; M R Scott |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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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:
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Created Date: 2000-01-05 Completed Date: 2000-01-05 Revised Date: 2009-11-18 |
Medline Journal Info:
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Nlm Unique ID: 7505876 Medline TA: Proc Natl Acad Sci U S A Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 14529-34 Citation Subset: IM |
Affiliation:
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Institute for Neurodegenerative Diseases, University of California, San Francisco, CA 94143-0518, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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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:
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AG02132/AG/NIA NIH HHS; AG08967/AG/NIA NIH HHS; NS14069/NS/NINDS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Polyamines; 0/Prions |
| Comments/Corrections | |
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