%0 Journal Article
%T Prions Ex Vivo: What Cell Culture Models Tell Us about Infectious Proteins
%A Sybille Krauss
%A Ina Vorberg
%J International Journal of Cell Biology
%D 2013
%I Hindawi Publishing Corporation
%R 10.1155/2013/704546
%X Prions are unconventional infectious agents that are composed of misfolded aggregated prion protein. Prions replicate their conformation by template-assisted conversion of the endogenous prion protein PrP. Templated conversion of soluble proteins into protein aggregates is also a hallmark of other neurodegenerative diseases. Alzheimer¡¯s disease or Parkinson¡¯s disease are not considered infectious diseases, although aggregate pathology appears to progress in a stereotypical fashion reminiscent of the spreading behavior ofmammalian prions. While basic principles of prion formation have been studied extensively, it is still unclear what exactly drives PrP molecules into an infectious, self-templating conformation. In this review, we discuss crucial steps in the life cycle of prions that have been revealed in ex vivo models. Importantly, the persistent propagation of prions in mitotically active cells argues that cellular processes are in place that not only allow recruitment of cellular PrP into growing prion aggregates but also enable the multiplication of infectious seeds that are transmitted to daughter cells. Comparison of prions with other protein aggregates demonstrates that not all the characteristics of prions are equally shared by prion-like aggregates. Future experiments may reveal to which extent aggregation-prone proteins associated with other neurodegenerative diseases can copy the replication strategies of prions. 1. Prions¡ªInfectious Agents Composed Predominately of Protein Prion diseases or transmissible spongiform encephalopathies (TSEs) are invariably fatal neurodegenerative diseases that are associated with severe spongiform vacuolation and nerve cell loss [1]. Animal and human TSEs are infectious diseases that either naturally spread between individuals of the same species or have been accidentally transmitted through food contaminants, blood and medical products, or during surgery [1]. Animal prion diseases include scrapie in sheep and goats, bovine spongiform encephalopathy, and chronic wasting disease in elk and deer [1]. TSEs in humans also occur sporadically or are of familial origin. Human prion diseases manifest as Creutzfeldt-Jakob disease, fatal familial insomnia, Gerstmann-Str£¿ussler-Scheinker syndrome and Kuru. Familial prion diseases are associated with dominantly inherited mutations in the coding region of the cellular prion protein. Many prion strains have also been successfully adapted to laboratory animals. Prion strains can be propagated in the same inbred mouse lines, where they produce phenotypically distinct
%U http://www.hindawi.com/journals/ijcb/2013/704546/