Propagated protein misfolding: New opportunities for therapeutics, new public health risk.

Abstract

There is now good consensus that propagated protein misfolding is the underlying mechanism for the infectious prion diseases (Creutzfeldt-Jakob disease in humans, scrapie in sheep and goats, bovine spongiform encephalopathy in cattle, and chronic wasting disease in deer and elk). Over the past decade it has become increasingly clear that other diseases, including Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis may progress via the same mechanism, involving a disease-specific polypeptide rather than the prion protein. Recent literature in these non-prion neurodegenerative diseases also points to the existence of multiple "strains" that express themselves differently in different contexts, resulting in different disease phenotypes. The probable cause of these neurodegenerative diseases is now referred to collectively as "propagated protein misfolding." Propagated protein misfolding raises many opportunities for new therapeutics and diagnostics. However, it also raises the theoretical risk of iatrogenic transmission, although experimental support for this notion is limited at present.