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PrPSc binding antibodies are potent inhibitors of prion replication in cell lines.

Beringue, V, Vilette, D, Mallinson, G, Archer, F, Kaisar, M, Tayebi, M, Jackson, GS, Clarke, AR, Laude, H, Collinge, J and Hawke, S (2004) PrPSc binding antibodies are potent inhibitors of prion replication in cell lines. J Biol Chem, 279 (38). pp. 39671-39676.

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Abstract

Conversion of the cellular alpha-helical prion protein (PrP(C)) into a disease-associated isoform (PrP(Sc)) is central to the pathogenesis of prion diseases. Molecules targeting either normal or disease-associated isoforms may be of therapeutic interest, and the antibodies binding PrP(C) have been shown to inhibit prion accumulation in vitro. Here we investigate whether antibodies that additionally target disease-associated isoforms such as PrP(Sc) inhibit prion replication in ovine PrP-inducible scrapie-infected Rov cells. We conclude from these experiments that antibodies exclusively binding PrP(C) were relatively inefficient inhibitors of ScRov cell PrP(Sc) accumulation compared with antibodies that additionally targeted disease-associated PrP isoforms. Although the mechanism by which these monoclonal antibodies inhibit prion replication is unclear, some of the data suggest that antibodies might actively increase PrP(Sc) turnover. Thus antibodies that bind to both normal and disease-associated isoforms represent very promising anti-prion agents.

Item Type: Article
Authors :
NameEmailORCID
Beringue, VUNSPECIFIEDUNSPECIFIED
Vilette, DUNSPECIFIEDUNSPECIFIED
Mallinson, GUNSPECIFIEDUNSPECIFIED
Archer, FUNSPECIFIEDUNSPECIFIED
Kaisar, MUNSPECIFIEDUNSPECIFIED
Tayebi, Mm.tayebi@surrey.ac.ukUNSPECIFIED
Jackson, GSUNSPECIFIEDUNSPECIFIED
Clarke, ARUNSPECIFIEDUNSPECIFIED
Laude, HUNSPECIFIEDUNSPECIFIED
Collinge, JUNSPECIFIEDUNSPECIFIED
Hawke, SUNSPECIFIEDUNSPECIFIED
Date : 17 September 2004
Identification Number : https://doi.org/10.1074/jbc.M402270200
Uncontrolled Keywords : Animals, Antibodies, Monoclonal, Antibody Specificity, Cell Line, Mice, Mice, Mutant Strains, PrPC Proteins, PrPSc Proteins, Precipitin Tests, Protein Binding
Related URLs :
Depositing User : Symplectic Elements
Date Deposited : 17 May 2017 10:14
Last Modified : 17 May 2017 14:48
URI: http://epubs.surrey.ac.uk/id/eprint/826987

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