NR ATIG
AU Vetrugno,V.; Cardinale,A.; Filesi,I.; Mattei,S.; Sy,M.S.; Pocchiari,M.; Biocca,S.
TI KDEL tagged anti-prion scFvs inhibit scrapie infection in vitro
QU International Conference - Prion 2005: Between fundamentals and society's needs - 19.10.-21.10.2005, Congress Center Düsseldorf - Poster Session: Cell Biology of PrPc and PrPsc CELL-38
PT Konferenz-Poster
AB
Transmissible spongiform encephalopathies (TSEs) or prion diseases are fatal neurodegenerative disorders characterized by the conversion of the cellular prion protein (PrPc) into the infectious scrapie isoform (PrPsc). Recombinant antibodies have been proved to be a promising tool to delay and inhibit prion replication. 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 and to prevent PrPsc accumulation in scrapie exposed KDEL-8H4-PC12 cells*. Here we demonstrate, by mouse bioassay, that scrapie infectivity is also prevented in these cells. In mice intracerebrally injected with scrapie infected KDEL-8H4-NGF differentiated PC12 cells, no scrapie clinical symptoms, no neuropathological abnormality (i.e. brain lesion profile) and no cerebral accumulation of any pathological PrP species (i.e. in terms of PK resistance and electrophoretic profile) have been observed. Our findings indicate that intracellular retention in ER compartment of PrPc by KDEL signal may be a reliable innovative therapeutic strategy for prion diseases.
*Cardinale et al., (2005), J. Biol. Chem., 280, 685-694.
AD V.Vetrugno, M.Pocchiari, Department of Cell Biology and Neurosciences, Istituto Superiore di Sanita, 00161 Rome, Italy; A.Cardinale, IRCCS San Raffaele, Via dei Bonacolsi snc, 00163, Roma, Italy; I.Filesi, S.Mattei, S.Biocca, Department of Neuroscience, University of Tor Vergata, Via Montpellier 1, 00133 Roma, Italy; M.S.Sy, Institute of Pathology and Department of Neuroscience, School of Medicine Case Western Riserve University, Cleveland, Ohio 44120
SP englisch
PO Deutschland
EA Bild 1, Bild 2, Bild 3, Bild 4, Bild 5, Bild 6, Bild 7, Bild 8