Identifying therapeutic targets and treatments in model systems

Abstract

In this chapter, we describe current therapeutic targets for prion diseases. We focus on targets that have been validated in vitro and in vivo, leaving out a plethora of theoretic targets that still require validation. We also show how the development of improved model systems for the study of prion infection and neurotoxic mechanisms has enabled target identification. Some therapeutic targets are prion-specific, such as PrP^TSE, while others are shared by other neurodegenerative diseases, for example, autophagy, cholesterol and energy metabolism, and neuroinflammation. In vivo models are discussed, and a genetic model of Creutzfeldt-Jakob disease particularly well suited for evaluation of prophylactic intervention is described in more detail.

Keywords: Creutzfeldt–Jakob disease; cell models; drug development; mouse models; neurotoxicity; prion; protein misfolding; therapeutic targets.