The suppression of prion propagation using poly-l-lysine by targeting plasminogen that stimulates prion protein conversion

Chongsuk Ryou, William B. Titlow, Charles E. Mays, Younsoo Bae, Sehun Kim

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

Poly-l-lysine (PLL), a homopolymer of amino acid l-lysine (LL), has been frequently used for drug delivery. Here, we report that PLL is an effective agent to inhibit propagation of prions that cause fatal and incurable neurologic disorders in humans and animals, termed prion diseases. In our recent investigation on prion propagation facilitated by conversion of the cellular prion protein (PrP) to the misfolded, disease-associated PrP (PrPSc), we demonstrated that plasminogen stimulates PrP conversion as a cellular cofactor. In the current study, we targeted plasminogen using PLL and assessed its anti-prion efficacy. The results showed that PLL strongly inhibited PrPSc propagation in the cell-free, cell culture, and mouse models of prion disease. These results confirm the role of plasminogen in PrPSc propagation, validates plasminogen as a therapeutic target to combat prion disease, and suggests PLL as a potential anti-prion agent. Therefore, our study represents a proof-of-concept that targeting plasminogen, a cofactor for PrP conversion, using PLL results in suppression of prion propagation, which represents a successful translation of our understanding on details of prion propagation into a potential therapeutic strategy for prion diseases.

Original languageEnglish
Pages (from-to)3141-3149
Number of pages9
JournalBiomaterials
Volume32
Issue number11
DOIs
StatePublished - Apr 2011

Bibliographical note

Funding Information:
The authors thank Glenn Telling for providing Tg4112 mice, Linda Van Eldik for constructive suggestions, and Paula Thomason for editing this manuscript. This work was supported in part by NIH grant ( P20 RR 020171 ) and funds from the College of Medicine, University of Kentucky .

Keywords

  • Cofactor
  • Plasminogen
  • Poly-l-lysine
  • Prion conversion
  • Therapeutic target
  • Translational research

ASJC Scopus subject areas

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

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