Prions and peripheral nerves: a deadly rendezvous

Abstract

The infectious particle causing transmissible spongiform encephalopathy (TSE), a fatal neurodegenerative disease of humans and animals, has been termed prion. Its major component is an aggregated variant of the cellular prion protein, PrP(C). The main target of prion pathology is the central nervous system (CNS), yet most prion diseases are initiated or accompanied by prion replication at extracerebral locations, including secondary lymphoid organs, muscle and, in some instances, blood. How do prions travel from the periphery into the CNS? Is this an active or a passive process and does neuronal prion transport explain the long incubation times in prion diseases? Alternatively, if prion infectivity arises spontaneously in the CNS, as believed from sporadic Creutzfeldt-Jakob patients, how do prions manage to travel from the CNS into the periphery (e.g., spleen, muscle) of the infected host? The mechanisms of neuronal prion transport from the periphery into the CNS or vice versa are heavily investigated and debated but poorly understood. Although research in the past has accumulated knowledge on prion progression from the periphery to the brain, we are far from understanding the molecular mechanisms of neuronal prion transport.