| First Author | Kong Q | Year | 2013 |
| Journal | Cell Rep | Volume | 4 |
| Issue | 2 | Pages | 248-54 |
| PubMed ID | 23871665 | Mgi Jnum | J:201911 |
| Mgi Id | MGI:5516155 | Doi | 10.1016/j.celrep.2013.06.030 |
| Citation | Kong Q, et al. (2013) Thermodynamic stabilization of the folded domain of prion protein inhibits prion infection in vivo. Cell Rep 4(2):248-54 |
| abstractText | Prion diseases, or transmissible spongiform encephalopathies (TSEs), are associated with the conformational conversion of the cellular prion protein, PrP(C), into a protease-resistant form, PrP(Sc). Here, we show that mutation-induced thermodynamic stabilization of the folded, alpha-helical domain of PrP(C) has a dramatic inhibitory effect on the conformational conversion of prion protein in vitro, as well as on the propagation of TSE disease in vivo. Transgenic mice expressing a human prion protein variant with increased thermodynamic stability were found to be much more resistant to infection with the TSE agent than those expressing wild-type human prion protein, in both the primary passage and three subsequent subpassages. These findings not only provide a line of evidence in support of the protein-only model of TSEs but also yield insight into the molecular nature of the PrP(C)-->PrP(Sc) conformational transition, and they suggest an approach to the treatment of prion diseases. |
