Neuroendocrine cultured cells counteract persistent prion infection by down-regulation of PrP

Cell models for prion diseases are mainly of neuronal origin. However, the pathological isoform PrPSc of cellular prion protein (PrPc) and prion infectivity are found in a variety of extraneural tissues in prion diseases. Although many cell types are not able to propagate PrPSc, little is known about cellular mechanism counteracting prion infection. It is desirable to identify neuronal or non-neuronal cell models that restrict PrPSc generation or propagate PrPSc only transiently. Neuroendocrine cells are derived from tumours forming the interface between endocrine and nervous system. We investigated the susceptibility of such murine cell lines to prion infection, which were in principle able to transiently propagate PrPSc. Surprisingly and in contrast to neuronal cells prion infection was abrogated by rapid and PrPSc-specific down-regulation of PrPc expression upon exposure to prion-infected material. Cell lines described here provide novel models for studying PrPc regulation and intrinsic cellular defence mechanisms upon prion exposure. (C) 2008 Elsevier Inc. All rights reserved.