Paramithiotis E, Pinard M, Lawton T, LaBoissiere S, Leathers VL, Zou WQ, Estey LA, Lamontagne J, Lehto MT, Kondejewski LH, Francoeur GP, Papadopoulos M, Haghighat A, Spatz SJ, Head M, Will R, Ironside J, O'Rourke K, Tonelli Q, Ledebur HC, Chakrabartty A, Cashman NR. A prion protein epitope selective for the pathologically misfolded conformation. Nat Med. 2003 Jul;9(7):893-9. PubMed.
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New York University School of Medicine
The study by Paramithiotis and colleagues is meticulously performed and demonstrates that animals immunized with the Tyr-Tyr-Arg repeat motif of the prion protein (PrP) generate antibodies that selectively recognize the scrapie form of PrP. Surprisingly, this epitope appears to have several conformations, as indicated by the variable recognition profile of the monoclonal antibodies. Because this sequence of amino acids is likely to occur in some other proteins, it may diminish the therapeutic and diagnostic utility of these antibodies.
It will be interesting to determine if these conformation-selective antibodies are more efficacious therapeutically than are antibodies that recognize both PrPC and PrPSc, as previously reported by us and others.
View all comments by Einar SigurdssonUniversity of California, Irvine
This is an excellent paper; the data about the specificity of the antibody are quite convincing. The rationale behind the development of this antibody is clever, and the same general approach of misfolding-dependent "side-chain accessibility" may be applicable to other types of protein-misfolding diseases. It looks promising as a research tool and a diagnostic, and may have therapeutic utility depending on how future studies turn out.
View all comments by Charles GlabeMake a Comment
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