Abstract

Prion diseases are enigmatic, neurodegenerative disorders affecting several mammalian species.
The family of diseases include scrapie of sheep, bovine spongiform encephalopathy (BSE),
Creutzfeldt-Jakob disease (CJD) of humans and chronic wasting disease (CWD) in deer and elk.
Prion diseases are believed to be caused by the misfolding of an endogenous host protein and the
abnormal, protease-resistant isoform of this protein is suggested to represent the infectious entity.
Through many transmission experiments, we know much about the course of prion diseases and
the ensuing pathology in the central nervous system. However, few of the causative mechanisms
have been deciphered at a level that allows prediction of the disease characteristics of novel prion
strains or that allows rational design of chemo-therapeutics. This review article outlines the state
of our knowledge of prion disease mechanisms from the concept of protein misfolding, through
the factors that may encode different strains of disease, mechanisms of neuronal loss and the ways
that disease are transmitted.