title: The 37 kDa/67 kDa laminin receptor is required for PrP(Sc) propagation in scrapie-infected neuronal cells.
abstract: The accumulation of PrP(Sc) in scrapie-infected neuronal cells has been prevented by three approaches: (i) transfection of ScMNB cells with an antisense laminin receptor precursor (LRP) RNA-expression plasmid, (ii) transfection of ScN2a cells and ScGT1 cells with small interfering RNAs (siRNAs) specific for the LRP mRNA, and (iii) incubation of ScN2a cells with an anti-LRP/LR antibody. LRP antisense RNA and LRP siRNAs reduced LRP/LR expression and inhibited the accumulation of PrP(Sc) in these cells. The treatments also reduced PrP(c) levels. The anti-LRP/LR antibody, W3, abolished PrP(Sc) accumulation and reduced PrP(c) levels after seven days of incubation. Cells remained free of PrP(Sc) after being cultured for 14 additional days without the antibody, whereas the PrP(c) level was restored. Our results demonstrate the necessity of the laminin receptor (LRP/LR) for PrP(Sc) propagation in cultured cells and suggest that LRP/LR-specific antibodies could be used as powerful therapeutic tools in the treatment of transmissible spongiform encephalopathies.
authors.affiliation: Laboratorium für Molekulare Biologie-Genzentrum-Institut für Biochemie der LMU München, Feodor-Lynen Str. 25, D- 81377 Munich, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Leucht
authors.forename: Steve
authors.initials: S
authors.lastname: Simoneau
authors.forename: Clémence
authors.initials: C
authors.lastname: Rey
authors.forename: Karen
authors.initials: K
authors.lastname: Vana
authors.forename: Roman
authors.initials: R
authors.lastname: Rieger
authors.forename: Corinne Ida
authors.initials: CI
authors.lastname: Lasmézas
authors.forename: Stefan
authors.initials: S
authors.lastname: Weiss
mesh_terms: D000818:Animals; D001692:Biological Transport; D008970:Molecular Weight; D009447:Neuroblastoma; D009474:Neurons / Q000378:metabolism*; D018620:PrPSc Proteins / Q000235:genetics / Q000378:metabolism*; D016372:RNA, Antisense / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000494:pharmacology; D017474:Receptors, Laminin / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012260:Ribonucleases; D012608:Scrapie / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D018620:PrPSc Proteins; D016372:RNA, Antisense; D034741:RNA, Small Interfering; D017474:Receptors, Laminin; D012260:Ribonucleases