Type I interferon protects neurons from prions in in vivo models

Ishibashi, Daisuke; Homma, Takujiro; Nakagaki, Takehiro; Fuse, Takayuki; Sano, Kazunori; Satoh, Katsuya; Mori, Tsuyoshi; Atarashi, Ryuichiro; Nishida, Noriyuki

Human prion diseases, including Creutzfeldt-Jakob disease, are transmissible neurodegenerative disorders for which no effective treatment is currently available. Prions are proteinaceous infectious pathogens distinct from bacteria or viruses. Accumulation of the structurally abnormal prion protein (PrP Sc ) causes pathological changes such as neuronal death in the brain, resulting in rapidly progressive cognitive disorders. PrP Sc , which is highly enriched in b-sheet secondary structures, causes misfolding of normal cellular PrP (PrP C ) (Prusiner, 1998; Weissmann et al., 2002) . In a widely-accepted model of the molecular mechanism of prion pathogenesis, following the expression or introduction of PrP Sc , the pathogenic proteins accumulate in and on neurons; subsequently, various inflammatory responses occur and induce neuronal death (Tamguney et al., 2008; Aguzzi et al., 2013) . One pathological feature associated with prion infection is widespread diffuse gliosis. However, the host-pathogen interaction in these diseases remains incompletely understood.