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Detection of Ctm-PrP and Dpl in TSE models

A publication from the group of DA Harris (Mutational analysis of topological determinants in prion protein (PrP) and measurement of transmembrane and cytosolic PrP during prion infection. J Biol Chem. 278, 45960-8) demonstrated that Ctm PrP was not directly involved in Prion neurodegeneration, both in infectious and genetic TSEs . Since detection of ctm-PrP was rather challenging we decided to focus more on Dpl.

We studied the cell biology of Doppel and the relationship between Doppel expression and PrPSc generation in both cultured cells and in the brain of CJD patients. This work revealed that Doppel expression (mRNA and protein levels) was not modified during prion replication. In addition over-expression of Doppel in infected cell cultures did not modified PrPSc generation and no proteinase K resistant Doppel could be detected in these cells. Overall, we have to conclude, as suggested previously in Doppel -/- transgenic animals, that Doppel does not influence prion propagation and does not seem involved in prion neuropathology.

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