We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Recombinant Human Prion Protein Inhibits Prion Propagation in vitro.
- Authors
Jue Yuan; Yi-An Zhan; Abskharon, Romany; Xiangzhu Xiao; Martinez, Manuel Camacho; Xiaochen Zhou; Kneale, Geoff; Mikol, Jacqueline; Lehmann, Sylvain; Surewicz, Witold K.; Castilla, Joaquín; Steyaert, Jan; Shulin Zhang; Qingzhong Kong; Petersen, Robert B.; Wohlkonig, Alexandre; Wen-Quan Zou
- Abstract
Prion diseases are associated with the conformational conversion of the cellular prion protein (PrPC) into the pathological scrapie isoform (PrPSc) in the brain. Both the in vivo and in vitro conversion of PrPC into PrPSc is significantly inhibited by differences in amino acid sequence between the two molecules. Using protein misfolding cyclic amplification (PMCA), we now report that the recombinant full-length human PrP (rHuPrP23-231) (that is unglycosylated and lacks the glycophosphatidylinositol anchor) is a strong inhibitor of human prion propagation. Furthermore, rHuPrP23-231 also inhibits mouse prion propagation in a scrapie-infected mouse cell line. Notably, it binds to PrPSc, but not PrPC, suggesting that the inhibitory effect of recombinant PrP results from blocking the interaction of brain PrPC with PrPSc. Our findings suggest a new avenue for treating prion diseases, in which a patient's own unglycosylated and anchorless PrP is used to inhibit PrPSc propagation without inducing immune response side effects
- Subjects
PRION diseases; SCRAPIE; AMINO acid sequence; CELL lines; IMMUNE response
- Publication
Scientific Reports, 2013, p1
- ISSN
2045-2322
- Publication type
Article
- DOI
10.1038/srep02911