Ovine recombinant PrP as an inhibitor of ruminant prion propagation in vitro

Maddison, Ben C.; Workman, Robert G.; Gough, Kevin C.

Abstract

Prion diseases are fatal and incurable neurodegenerative diseases of humans and animals. Despite years of research, no therapeutic agents have been developed that can effectively manage or reverse disease progression. Recently it has been identified that recombinant prion proteins (rPrP) expressed in bacteria can act as inhibitors of prion replication within the in vitro prion replication system Protein Misfolding Cyclic Amplification (PMCA). Here, within PMCA reactions amplifying a range of ruminant prions including distinct Prnp genotypes/host species and distinct prion strains, recombinant ovine VRQ PrP displayed consistent inhibition of prion replication and produced IC50 values of 122 and 171 nM for ovine scrapie and bovine BSE replication, respectively. These findings illustrate the therapeutic potential of rPrPs with distinct TSE diseases.

Citation

Maddison, B. C., Workman, R. G., & Gough, K. C. (in press). Ovine recombinant PrP as an inhibitor of ruminant prion propagation in vitro. Prion, 11(4), https://doi.org/10.1080/19336896.2017.1342919

• Journal Article Type: Article
• Acceptance Date: Jun 12, 2017
• Online Publication Date: Jun 30, 2017
• Deposit Date: Jun 21, 2017
• Publicly Available Date: Jun 30, 2017
• Journal: Prion
• Print ISSN: 1933-6896
• Electronic ISSN: 1933-690X
• Publisher: Taylor and Francis
• Peer Reviewed: Peer Reviewed
• Volume: 11
• Issue: 4
• DOI: https://doi.org/10.1080/19336896.2017.1342919
• Keywords: Scrapie, BSE, Recombinant PrP, prion diseases, PMCA, Protein inhibitors, Therapeutics
• Public URL: https://nottingham-repository.worktribe.com/output/870614
• Publisher URL: http://www.tandfonline.com/doi/full/10.1080/19336896.2017.1342919
• Contract Date: Jun 21, 2017