RESUMEN
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.
Asunto(s)
Síndrome de Creutzfeldt-Jakob/genética , Enfermedad de Gerstmann-Straussler-Scheinker/genética , Gripe Humana/genética , Insomnio Familiar Fatal/genética , Proteínas PrPC/genética , Proteínas PrPSc/genética , Proteínas Priónicas/genética , Animales , Línea Celular Tumoral , Síndrome de Creutzfeldt-Jakob/metabolismo , Síndrome de Creutzfeldt-Jakob/patología , Síndrome de Creutzfeldt-Jakob/virología , Enfermedad de Gerstmann-Straussler-Scheinker/metabolismo , Enfermedad de Gerstmann-Straussler-Scheinker/patología , Enfermedad de Gerstmann-Straussler-Scheinker/virología , Humanos , Virus de la Influenza A/genética , Virus de la Influenza A/crecimiento & desarrollo , Virus de la Influenza A/patogenicidad , Gripe Humana/metabolismo , Gripe Humana/patología , Gripe Humana/virología , Insomnio Familiar Fatal/metabolismo , Insomnio Familiar Fatal/patología , Insomnio Familiar Fatal/virología , Ratones , Ratones Transgénicos , Mutación , Neuronas/metabolismo , Neuronas/patología , Neuronas/virología , Proteínas PrPC/química , Proteínas PrPC/metabolismo , Proteínas PrPSc/química , Proteínas PrPSc/metabolismo , Proteínas Priónicas/química , Proteínas Priónicas/metabolismo , Conformación Proteica , Genética Inversa/métodosRESUMEN
The prion diseases or transmissible spongiform encephalopathies (TSE) constitute a group of hereditary or acquired neurodegenerative disorders. The Authors evaluate the etiopathogenetic background, the clinical features and the current concerns with special attention to bovine spongiform encephalopathy and new variant Creutzfeldt Jacob disease.