Transport of Prions in the Peripheral Nervous System: Pathways, Cell Types, and Mechanisms

Abstract

Prion diseases are transmissible protein misfolding disorders that occur in animals and humans where the endogenous prion protein, PrPC, undergoes a conformational change into self-templating aggregates termed PrPSc. Formation of PrPSc in the central nervous system (CNS) leads to gliosis, spongiosis, and cellular dysfunction that ultimately results in the death of the host. The spread of prions from peripheral inoculation sites to CNS structures occurs through neuroanatomical networks. While it has been established that endogenous PrPC is necessary for prion formation, and that the rate of prion spread is consistent with slow axonal transport, the mechanistic details of PrPSc transport remain elusive. Current research endeavors are primarily focused on the cellular mechanisms of prion transport associated with axons. This includes elucidating specific cell types involved, subcellular machinery, and potential cofactors present during this process.