Modeling the Cell Biology of Prions

Cell models have been useful for elucidating the function of proteins and/or their role in pathogenesis. Even before the discovery that the prion protein was a normal cellular protein (Oesch et al., Cell 40:735-746, 1985), cell models were developed to investigate prion infection (Rubenstein et al., J Gen Virol 65:2191-2198, 1984). Subsequently, with the discovery of familial forms of human prion diseases (Hsiao et al., Nature 338:342-345, 1989), cell models were developed to investigate the effect of mutations on the metabolism of the prion protein and, in parallel, the normal synthesis and processing of the cellular prion protein. In this chapter, we review the progress made in these two areas to date.