The term “prion” was originally coined by Prusiner to explain the unusual infectious agent in transmissible spongiform encephalopathies (TSEs, also known as prion disease). Now the term has expanded to include a growing list of fungal proteins that stably maintain an atypical self-propagating conformation and epigenetically modify a variety of cellular processes. Although fungal prions and the TSE agent share the capability of maintaining an atypical self-propagating conformation, fungal prions distinctly differ from the TSE agent in several aspects. Thus far, the TSE agent is the only prion that behaves as a bona fide infectious agent, having an infectious cycle, capable of transmitting horizontally (among a community) and causing epidemic outbreaks.
A key concept of the prion hypothesis is that prion is a self-propagating PrP conformer, which elicits the conversion of host-encoded normal PrPC to pathogenic PrPSc. Polyanions, such as RNA molecules and proteoglycans, have been identified as one type of cofactors in the brain homogenate that enhance prion propagation. Lipids are another type of cofactors that promote prion propagation in cell-free conversion assay and in propagating recombinant prions.