Abstract
Conformational conversion of the cellular isoform of prion protein, PrPC, into the abnormally folded, amyloidogenic isoform, PrPSc, is an underlying pathogenic mechanism in prion diseases. The diseases manifest as sporadic, hereditary, and acquired disorders. Etiological mechanisms driving the conversion of PrPC into PrPSc are unknown in sporadic prion diseases, while prion infection and specific mutations in the PrP gene are known to cause the conversion of PrPC into PrPSc in acquired and hereditary prion diseases, respectively. We recently reported that a neurotropic strain of influenza A virus (IAV) induced the conversion of PrPC into PrPSc as well as formation of infectious prions in mouse neuroblastoma cells after infection, suggesting the causative role of the neuronal infection of IAV in sporadic prion diseases. Here, we discuss the conversion mechanism of PrPC into PrPSc in different types of prion diseases, by presenting our findings of the IAV infection-induced conversion of PrPC into PrPSc and by reviewing the so far reported transgenic animal models of hereditary prion diseases and the reverse genetic studies, which have revealed the structure-function relationship for PrPC to convert into PrPSc after prion infection.
Highlights
Prion diseases, or transmissible spongiform encephalopathies, are a group of fatal neurodegenerative disorders in humans and animals, caused by accumulation of proteinaceous infectious particles, termed “prions”, in the brain [1,2,3]
The annual incidence of Sporadic Creutzfeldt-Jakob disease (sCJD) has been estimated to be 1–2 cases per a million people worldwide, the reported incidence varies from country to country and is influenced by the method and extent of the study conducted [7]. 10–15% of human cases belong to hereditary prion diseases, such as familial CJD, Gerstmann-Sträussler-Scheinker syndrome (GSS), and fatal familial insomnia (FFI) [8,9]
Cornea, and growth hormone from the patients, and depth electroencephalogram electrodes and neurosurgical instruments used for the patients have been considered to transmit the disease [11]. variant CJD (vCJD) is believed to be transmitted from bovine spongiform encephalopathy (BSE) via oral consumption of BSE prion-contaminated food [10]
Summary
Transmissible spongiform encephalopathies, are a group of fatal neurodegenerative disorders in humans and animals, caused by accumulation of proteinaceous infectious particles, termed “prions”, in the brain [1,2,3]. 10–15% of human cases belong to hereditary prion diseases, such as familial CJD (fCJD), Gerstmann-Sträussler-Scheinker syndrome (GSS), and fatal familial insomnia (FFI) [8,9]. They are causatively linked to specific mutations in the gene (Prnp) of prion protein (PrP) [8,9]. We review the so far reported transgenic (Tg) mouse models of hereditary prion diseases, where mutated PrPs are spontaneously converted into PrPScs, and the reverse genetic studies using Prnp0/0 mice, which have revealed the important regions for PrPC to convert into PrPSc after prion infection
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
