Mechanisms of prion toxicity and their relationship to prion infectivity

Abstract

According to the protein only hypothesis, an abnormal isoform of the host encoded prion protein (PrPC), referred to as PrPSc, is the sole or major component of the infectious agent the "prion" causing transmissible spongiform encephalopathies1. PrPC expression is required for PrPSc propagation and was definitively established by the resistance of PrP null mice to infectious prions2. PrP C is absolutely required for not only infectivity, but also PrP associated neurotoxicity3. This was demonstrated by grafting of embryonic telencephalic tissue from transgenic mice overexpressing PrP into the brains of PrP null mice and inoculating the PrP expressing graft with mice prions. The PrP expressing ..