The inhibition of prions through blocking prion conversion by permanently charged branched polyamines of low cytotoxicity

Yong beom Lim, Charles E. Mays, Younghwan Kim, William B. Titlow, Chongsuk Ryou

Research output: Contribution to journalArticlepeer-review

45 Citations (Scopus)


Branched polyamines are effective in inhibiting prions in a cationic surface charge density dependent manner. However, toxicity associated with branched polyamines, in general, often hampers the successful application of the compounds to treat prion diseases. Here, we report that constitutively maintained cationic properties in branched polyamines reduced the intrinsic toxicity of the compounds while retaining the anti-prion activities. In prion-infected neuroblastoma cells, quaternization of amines in polyethyleneimine (PEI) and polyamidoamine (PAMAM) dendrimers markedly increased the nontoxic concentration ranges of the compounds and still supported, albeit reduced, an appreciable level of anti-prion activity in clearing prions from the infected cells. Furthermore, quaternized PEI was able to degrade prions at acidic pH conditions and inhibit the in vitro prion propagation facilitated by conversion of the normal prion protein isoform to its misfolded counterpart, although such activities were decreased by quaternization. Quaternized PAMAM was least effective in degrading prions but efficiently inhibited prion conversion with the same efficacy as unmodified PAMAM. Our results suggest that quaternization represents an effective strategy for developing nontoxic branched polyamines with potent anti-prion activity. This study highlights the importance of polyamine structural control for developing polyamine-based anti-prion agents and understanding of an action mechanism of quaternized branched polyamines.

Original languageEnglish
Pages (from-to)2025-2033
Number of pages9
Issue number8
Publication statusPublished - 2010 Mar

Bibliographical note

Funding Information:
The authors thank Paula Thomason for editorial assistance. This work was supported in part by funds from the Sanders-Brown Center on Aging and College of Medicine, University of Kentucky (CR); and grants from the National Research Foundation of Korea (Grants-in-aid 2009-0066736, 2009-0076516, 2009-0082617), Translational Research Center for Protein Function Control (2009-0092971), and Priority Research Center (2009-0093823), Yonsei University (YL).

All Science Journal Classification (ASJC) codes

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials


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