Prions, prionoids and protein misfolding disorders

Prion diseases are progressive, incurable and fatal neurodegenerative conditions. The term ‘prion’ was first nominated to express the revolutionary concept that a protein could be infectious. We now know that prions consist of PrPSc, the pathological aggregated form of the cellular prion protein PrPC. Over the years, the term has been semantically broadened to describe aggregates irrespective of their infectivity, and the prion concept is now being applied, perhaps overenthusiastically, to all neurodegenerative diseases that involve protein aggregation. Indeed, recent studies suggest that prion diseases (PrDs) and protein misfolding disorders (PMDs) share some common disease mechanisms, which could have implications for potential treatments. Nevertheless, the transmissibility of bona fide prions is unique, and PrDs should be considered as distinct from other PMDs. Parallels are increasingly being drawn between prion diseases and other aggregate-mediated neurodegenerative disorders. While prion diseases are a distinct subclass of protein misfolding disorders (PMDs), a better understanding of shared mechanisms is likely to benefit treatment of all PMDs.