In vivo prion models and the disconnection between transmissibility and neurotoxicity

Abstract

The primary causative event in the development of prion diseases is the misfolding of the normal prion protein (PrPC) into an ensemble of altered conformers (herein collectively denoted as PrPSc) that accumulate in the brain. Prominent amongst currently unresolved key aspects underpinning prion disease pathogenesis is whether transmission and toxicity are sub-served by different molecular species of PrPSc, which may directly impact on the development of effective targeted treatments. The use of murine models of prion disease has been of fundamental importance for probing the relationship between hypothesised “neurotoxic” and “transmissible” PrPSc and the associated kinetic profiles of their ..