Anti-PrP antibodies block PrPSc replication in prion-infected cell cultures by accelerating PrPC degradation.
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 PrP(Sc) 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 PrP(Sc) formation in prion-infected neuroblastoma cells but also decreased the PrP(C) levels in non-infected N2a cells. In addition, treatment with both SAF34 and SAF61 antibodies decreased PrP(C) and PrP(Sc) 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 PrP(Sc) in cells is directly coupled to PrP(C) degradation by reducing the half-life of the PrP(C) protein.
Perrier
Véronique
V
Institut de Génétique Humaine, Montpellier, France. veronique.Perrier@igh.cnrs.fr
Solassol
Jérôme
J
Crozet
Carole
C
Frobert
Yveline
Y
Mourton-Gilles
Chantal
C
Grassi
Jacques
J
Lehmann
Sylvain
S
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D004357:Drug Synergism; D006801:Humans; D051379:Mice; D009447:Neuroblastoma / Q000188:drug therapy / Q000378:metabolism; D018621:PrPC Proteins / Q000276:immunology* / Q000378:metabolism*; D018620:PrPSc Proteins / Q000037:antagonists & inhibitors* / Q000276:immunology*; D017096:Prion Diseases / Q000276:immunology* / Q000628:therapy
D000911:Antibodies, Monoclonal; D018621:PrPC Proteins; D018620:PrPSc Proteins