NR AQNO
AU Perrier,V.; Solassol,J.; Crozet,C.A.; Frobert,Y.; Mourton-Gilles,C.; Grassi,J.; Lehmann,S.
TI Anti-PrP antibodies block PrPsc replication in prion-infected cell cultures by accelerating PrPc degradation
QU Journal of Neurochemistry 2004 Apr; 89(2): 454-63
PT journal article
AB The use of anti-PrP antibodies represents one of the most promising strategies for the treatment of prion diseases. In the present study, we screened various anti-PrP antibodies with the aim of identifying those that would block PrPsc replication in prion-infected cell culture. Two antibodies, SAF34 recognizing the flexible octarepeats region on HuPrP protein, and SAF61 directed against PrP amino acid residues (144-152), not only inhibited PrPsc formation in prion-infected neuroblastoma cells but also decreased the PrPc levels in non-infected N2a cells. In addition, treatment with both SAF34 and SAF61 antibodies decreased PrPc and PrPsc levels in the cells synergistically. In the presence of both antibodies, our results showed that the mode of action which leads to the disappearance of PrPsc in cells is directly coupled to PrPc degradation by reducing the half-life of the PrPc protein.
MH Animals; Antibodies, Monoclonal/*pharmacology; Cell Line, Tumor; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Drug Synergism; Human; Mice; Neuroblastoma/drug therapy/metabolism; PrPc Proteins/*immunology/*metabolism; PrPsc Proteins/*antagonists & inhibitors/*immunology; Prion Diseases/*immunology/therapy
AD Véronique Perrier (veronique.Perrier@igh.cnrs.fr), Jérome Solassol, Carole Crozet, Sylvain Lehmann, Institut de Génétique Humaine, Montpellier, France; Yveline Frobert, Jacques Grassi, CEA Saclay, DRM/SPI, Gifsur Yvette, France; Chantal Mourton-Gilles, CNRS UMR 5094, Faculté de Pharmacie, Montpellier, France
SP englisch
PO England