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Factors influencing Ctm-PrP generation

While setting up the tools to work with Ctm-PrP it was demonstrated that this molecule is not a major determinant in Neurodegeneration but rather a by-product which study is valid especially if interested in translation phenomenon. On the other hand, new studies from the groups of S. Lindquist, A. Taraboulos and C. Soto put forward the idea that proteasomal degradation, the endoplasmic reticulum and generation of a cytosoloic form of PrP could play an essential role in prion pathology. In a previous work, we suggested that PrP can be subjected to retrograde transport toward the endoplasmic reticulum and that this compartment may play a significant role in PrPSc conversion. We also recently observed that PrPSc can be readily detected in the nucleus of infected cells, associated to DNA. Taking in account all these data, we are now looking in parallel at the consequences of the expression of wild-type, cytosolic, transmembrane and nuclear PrPs in neuronal cells.

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