Differential solubility of prions is associated in manifold phenotypes

The main feature of prion diseases is the accumulation of infectious proteins (PrPSc). Since PrPSc results from conversion of cellular prion proteins (PrPC), differential expressed PrPC types may play an important role in the formation and conversion efficiency to specific PrPSc forms. However, little is known about the PrPC expression, regulation and differentiation. Here, we demonstrate a new type of differentiation of overlapping PrPC isoforms in brain homogenates using differential SDS solubility. Low and highly soluble PrPC were detected along with various types of protein which are present in the brain of non-infected humans, sheep and cattle. Our findings provide evidence for the existence of several overlapping PrPC proteins exhibiting distinct glycotypes. The selection of defined PrPC types offers new possibilities for identifying highly efficient converting proteins and provides the potential for disease control.