prenions

Prenions are a proposed class of misfolded prion protein conformers that are believed to arise in the early stages of prion disease before the appearance of infectious prions. The term is not widely used in the mainstream literature and remains largely theoretical. In this framework, the normal cellular prion protein (PrPC) can adopt intermediate misfolded states that lack the stable self-propagating properties of PrPSc, the infectious isoform. Prenions would be short-lived or less stable species that may nonetheless influence disease progression by altering aggregation pathways or acting as seeds for later conversion.

The concept serves to describe an intermediate continuum in prion protein misfolding rather than a distinct, transmissible agent. Because prenions, by definition, do not yet exhibit efficient templated replication, evidence for them is indirect and contested. Researchers rely on sensitive in vitro amplification assays and advanced biophysical techniques to detect early conformational changes in PrP, but distinguishing prenions from early PrPSc or other aggregates remains challenging. Consequently, prenions are considered speculative rather than established entities.

If valid, the prenion concept could help explain variability in incubation periods and tissue tropism by highlighting early conformational states that predispose PrP to misfolding. It could also inform diagnostic strategies aimed at detecting disease-associated PrP before infectious prions emerge. More systematic studies are needed to determine whether prenions are real intermediates, their properties, and their relevance to disease.