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De novo mammalian prion synthesis

Prions are responsible for a heterogeneous group of fatal neurodegenerative diseases. They can manifest as infectious, sporadic or genetic disorders involving posttranslational modifications of the cellular prion protein (PrPC). Prions (PrPSc) are characterized by their infectious property and intrinsic ability to convert the physiological PrPC into the pathological form, acting as a template. The “protein-only” hypothesis, postulated by Stanley B. Prusiner, implies the possibility to generate de novo prions in vivo and in vitro. Here we will describe major milestones towards proving this hypothesis, taking into account physiological environment/s, biochemical properties and interactors of the PrPC.