Prion Protein Interactions with Nucleic Acid: Possible Models for Prion Disease and Prion Function

Several models for the transmission and progression of prion diseases have arisen, evolving with the acquisition of new experimental results. It is generally accepted that the PrPSc protein is at least part of the infectious particle and the major protein component of the scrapie-associated fibrils (SAFs) that characterize the disease. An additional, unknown cofactor is most likely involved in transmission of the disease, perhaps by influencing the PrPC → PrPSc transition. This review relates experimental observations on the interactions of nucleic acids (NAs) and PrP with specific focus on alterations in structure. In particular, NAs appear to induce PrPC to acquire some of the structural and biochemical characteristics of PrPSc. An updated hypothesis is related wherein NAs, on the basis of their structure, act in the PrPC → PrPSc transformation by serving as catalysts and/or chaperones and not by encoding genetic information.