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Solforosi L, Criado JR, McGavern DB, Wirz S, Sánchez-Alavez M, Sugama S, Degiorgio LA, Volpe BT, Wiseman E, Abalos G, Masliah E, Gilden D, Oldstone MB, Conti B, Williamson RA. Cross-linking cellular prion protein triggers neuronal apoptosis in vivo. Science. 2004 Mar 5;303(5663):1514-6. PubMed.
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University of Texas Medical School at Houston
In this intriguing article, Solforosi and coworkers show that intracerebral injection of certain anti-PrP monoclonal antibodies produce neuronal apoptosis. The author's interpretation is that crosslinking several molecules of PrPc with the antibody is responsible for this effect. The data provided is clean and the controls are appropriate.
It would be interesting to investigate further the relationship of these findings to the disease process. One way to approach this would be to study in more detail whether the characteristics of neuronal damage induced by antibody crosslinking are the same as those produced by prion infection.
An alternative interpretation for the need for crosslinking could be that certain antibodies produce a specific conformational change, or block the interaction of PrP with another protein (something that cannot be mimicked by the Fab fragment alone). Whether this is what happens during PrPSc-PrPc interaction is unknown, but is an interesting possibility to explore.
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