Electrophysiological Investigations of Prion Protein Roles in Health and Disease

Abstract

Prion diseases are transmissible and fatal neurological disorders associated with the misfolding of cellular prion protein (PrPC) into disease-causing isoforms (PrPD) in the central nervous system. The diseases have three etiologies; acquired through exposure to the infectious PrPD, sporadic, arising from no known cause, and hereditary due to familial mutations within the PRNP gene. The manifestation of clinical signs is associated with the disruption of neuronal activity and subsequent degeneration of neurons. To generate insight into the mechanisms by which neuronal activity becomes disrupted in prion diseases, electrophysiological techniques have been applied to closely study the electrical signaling properties of neurons that lack functional PrPC as well as neurons that are developing pathological features of prion diseases due to infection or genetic mutation. In this review, we will compile the electrophysiological evidences of neurophysiological roles of PrPC, how those roles are changed in neurons that are developing prion diseases, and how disease-associated effects are exacerbated during the clinical stage of disease.