title: Immunomodulation of the human prion peptide 106-126 aggregation.
abstract: Site-directed monoclonal antibodies (mAbs) may interact with their antigens, leading to stabilization, refolding, and suppression of aggregation. In the following study, we show that mAbs raised against the peptide 106-126 of human prion protein (PrP 106-126) modulate the conformational changes occurring in the peptide exposed to aggregation conditions. MAbs 3-11 and 2-40 prevent PrP 106-126's fibrillar aggregation, disaggregates already formed aggregates, and inhibits the peptide's neurotoxic effect on the PC12 cells system, while mAb 3F4 has no protective effect. We suggest that there are key positions within the PrP 106-126 molecule where unfolding is initiated and their locking with specific antibodies may maintain the prion peptide native structure, reverse the aggregated peptide conformation, and lead to rearrangements involved in the essential feature of prion diseases.
authors.affiliation: Department of Molecular Microbiology and Biotechnology, Faculty of Life Sciences, Ramat Aviv, Tel-Aviv 69978, Israel.
authors.forename: E
authors.initials: E
authors.lastname: Hanan
authors.forename: O
authors.initials: O
authors.lastname: Goren
authors.forename: M
authors.initials: M
authors.lastname: Eshkenazy
authors.forename: B
authors.initials: B
authors.lastname: Solomon
mesh_terms: D000682:Amyloid / Q000737:chemistry / Q000187:drug effects; D000818:Animals; D000911:Antibodies, Monoclonal; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D009498:Neurotoxins / Q000633:toxicity; D016716:PC12 Cells; D010446:Peptide Fragments / Q000737:chemistry* / Q000276:immunology* / Q000633:toxicity; D011328:Prions / Q000737:chemistry* / Q000276:immunology* / Q000633:toxicity; D011487:Protein Conformation; D011489:Protein Denaturation; D051381:Rats
chemical_list: D000682:Amyloid; D000911:Antibodies, Monoclonal; D009498:Neurotoxins; D010446:Peptide Fragments; D011328:Prions; C082632:prion protein (106-126)