DOI: 10.1128/jvi.75.7.3453-3461.2001. Branched Polyamines Cure Prion-Infected Neuroblastoma Cells

Branched Polyamines Cure Prion-Infected Neuroblastoma Cells

10.1128/jvi.75.7.3453-3461.2001

Crossref journal-article

American Society for Microbiology

Journal of Virology (235)

Abstract

ABSTRACT Branched polyamines, including polyamidoamine and polypropyleneimine (PPI) dendrimers, are able to purge PrP Sc , the disease-causing isoform of the prion protein, from scrapie-infected neuroblastoma (ScN2a) cells in culture (S. Supattapone, H.-O. B. Nguyen, F. E. Cohen, S. B. Prusiner, and M. R. Scott, Proc. Natl. Acad. Sci. USA 96:14529–14534, 1999). We now demonstrate that exposure of ScN2a cells to 3 μg of PPI generation 4.0/ml for 4 weeks not only reduced PrP Sc to a level undetectable by Western blot but also eradicated prion infectivity as determined by a bioassay in mice. Exposure of purified RML prions to branched polyamines in vitro disaggregated the prion rods, reduced the β-sheet content of PrP 27-30, and rendered PrP 27-30 susceptible to proteolysis. The susceptibility of PrP Sc to proteolytic digestion induced by branched polyamines in vitro was strain dependent. Notably, PrP Sc from bovine spongiform encephalopathy-infected brain was susceptible to PPI-mediated denaturation in vitro, whereas PrP Sc from natural sheep scrapie-infected brain was resistant. Fluorescein-labeled PPI accumulated specifically in lysosomes, suggesting that branched polyamines act within this acidic compartment to mediate PrP Sc clearance. Branched polyamines are the first class of compounds shown to cure prion infection in living cells and may prove useful as therapeutic, disinfecting, and strain-typing reagents for prion diseases.

Bibliography

Supattapone, S., Wille, H., Uyechi, L., Safar, J., Tremblay, P., Szoka, F. C., Cohen, F. E., Prusiner, S. B., & Scott, M. R. (2001). Branched Polyamines Cure Prion-Infected Neuroblastoma Cells. Journal of Virology, 75(7), 3453â3461.

Authors 9

Surachai Supattapone (first)
Holger Wille (additional)
Lisa Uyechi (additional)
Jiri Safar (additional)
Patrick Tremblay (additional)
Francis C. Szoka (additional)
Fred E. Cohen (additional)
Stanley B. Prusiner (additional)
Michael R. Scott (additional)

References 38 Referenced 180

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Dates

Type	When
Created	23 years, 1 month ago (July 27, 2002, 5:55 a.m.)
Deposited	3 years, 6 months ago (March 5, 2022, 1:48 a.m.)
Indexed	3 months ago (June 4, 2025, 6:05 a.m.)
Issued	24 years, 5 months ago (April 1, 2001)
Published	24 years, 5 months ago (April 1, 2001)
Published Print	24 years, 5 months ago (April 1, 2001)

Funders 0

None

BibTeX

@article{Supattapone_2001, title={Branched Polyamines Cure Prion-Infected Neuroblastoma Cells}, volume={75}, ISSN={1098-5514}, url={http://dx.doi.org/10.1128/jvi.75.7.3453-3461.2001}, DOI={10.1128/jvi.75.7.3453-3461.2001}, number={7}, journal={Journal of Virology}, publisher={American Society for Microbiology}, author={Supattapone, Surachai and Wille, Holger and Uyechi, Lisa and Safar, Jiri and Tremblay, Patrick and Szoka, Francis C. and Cohen, Fred E. and Prusiner, Stanley B. and Scott, Michael R.}, year={2001}, month=apr, pages={3453–3461} }

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  "abstract": "<jats:title>ABSTRACT</jats:title>\n          <jats:p>\n            Branched polyamines, including polyamidoamine and polypropyleneimine (PPI) dendrimers, are able to purge PrP\n            <jats:sup>Sc</jats:sup>\n            , the disease-causing isoform of the prion protein, from scrapie-infected neuroblastoma (ScN2a) cells in culture (S. Supattapone, H.-O. B. Nguyen, F. E. Cohen, S. B. Prusiner, and M. R. Scott, Proc. Natl. Acad. Sci. USA 96:14529\u201314534, 1999). We now demonstrate that exposure of ScN2a cells to 3 \u03bcg of PPI generation 4.0/ml for 4 weeks not only reduced PrP\n            <jats:sup>Sc</jats:sup>\n            to a level undetectable by Western blot but also eradicated prion infectivity as determined by a bioassay in mice. Exposure of purified RML prions to branched polyamines in vitro disaggregated the prion rods, reduced the \u03b2-sheet content of PrP 27-30, and rendered PrP 27-30 susceptible to proteolysis. The susceptibility of PrP\n            <jats:sup>Sc</jats:sup>\n            to proteolytic digestion induced by branched polyamines in vitro was strain dependent. Notably, PrP\n            <jats:sup>Sc</jats:sup>\n            from bovine spongiform encephalopathy-infected brain was susceptible to PPI-mediated denaturation in vitro, whereas PrP\n            <jats:sup>Sc</jats:sup>\n            from natural sheep scrapie-infected brain was resistant. Fluorescein-labeled PPI accumulated specifically in lysosomes, suggesting that branched polyamines act within this acidic compartment to mediate PrP\n            <jats:sup>Sc</jats:sup>\n            clearance. Branched polyamines are the first class of compounds shown to cure prion infection in living cells and may prove useful as therapeutic, disinfecting, and strain-typing reagents for prion diseases.\n          </jats:p>",
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