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EnglishTransmissible spongiform encephalopathy or prion diseases are fatal neurodegenerative disorders characterized by the conversion of the cellular prion protein (PrPC) into the infectious scrapie isoform. (PrPSc). We have recently demonstrated that anti-prion intrabodies targeted to the lumen of the endoplasmic reticulum provide a simple and effective means to inhibit the transport of PrPC to the cell surface. Here, we report that they completely block the traffic of mature full-length PrPC molecules, impair prion lysosomal degradation, and interfere with the early phase of scrapie formation. Since anti-prion intrabodies efficiently block PrPSc accumulation in vitro, we investigated whether they could also antagonize scrapie infectivity in vivo. We found that mice intracerebrally injected with KDEL-8H4-NGF-differentiated PC12 cells infected with scrapie neither develop scrapie clinical signs nor brain damage. Furthermore, no protease-resistant PrPSc is detectable in brains of inoculated animals. These results indicate that anti-prion intrabody strategy may be effective against prion infection. (c) 2005 Elsevier Inc. All rights reserved.
Vetrugno, V., Cardinale, A., Filesi, I., Mattei, S., Sy, M., Pocchiari, M., et al. (2005). KDEL-tagged anti-prion intrabodies impair PrP lysosomal degradation and inhibit scrapie infectivity. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 338(4), 1791-1797.
| Tipologia: | Articolo su rivista |
| Citazione: | Vetrugno, V., Cardinale, A., Filesi, I., Mattei, S., Sy, M., Pocchiari, M., et al. (2005). KDEL-tagged anti-prion intrabodies impair PrP lysosomal degradation and inhibit scrapie infectivity. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 338(4), 1791-1797. |
| IF: | Con Impact Factor ISI |
| Lingua: | English |
| Settore Scientifico Disciplinare: | Settore BIO/12 |
| Revisione (peer review): | Sì, ma tipo non specificato |
| Tipo: | Articolo |
| Rilevanza: | Rilevanza internazionale |
| Digital Object Identifier (DOI): | http://dx.doi.org/10.1016/j.bbrc.2005.10.146 |
| Stato di pubblicazione: | Pubblicato |
| Data di pubblicazione: | 2005 |
| Titolo: | KDEL-tagged anti-prion intrabodies impair PrP lysosomal degradation and inhibit scrapie infectivity |
| Autori: | |
| Autori: | Vetrugno, V; Cardinale, A; Filesi, I; Mattei, S; Sy, M.-S; Pocchiari, M; Biocca, S |
| Appare nelle tipologie: | 01 - Articolo su rivista |
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