NR ATGA
AU Lehmann,S.L.; Casanova,D.; Milhavet,O.
TI Neural stem cells can propagate prions in culture
QU International Conference - Prion 2005: Between fundamentals and society's needs - 19.10.-21.10.2005, Congress Center Düsseldorf - Oral sessions ORAL-31
PT Konferenz-Vortrag
AB
The abnormal prion protein (PrPsc) plays a central role in the transmission of prion diseases. Accumulation of PrPsc in the central nervous system (CNS) leads to neurodegeneration with neuronal cell death and gliosis. Until now, only few cell culture systems able to convert the prion protein into its pathologic isoform have been established. Moreover, these systems are in most cases, only susceptible to a limited number of strains and unable to convert heterologous prions according to the species cross-barrier.
CNS neural stem cells (NSC) are the self-renewing, multipotent cells that generate neurons, astrocytes, and oligodendrocytes in the nervous system. We hypothesized that NSC could be highly permissive to prions. This led us to establish a new versatile cell culture system based on these cells. NSC from fetal and adult origins were indeed able to produce de novo PrPsc following exposure to prions from different strains and species. The transmissible nature of the newly produced PrPsc was demonstrated by transmission of PrPsc production from an infected cell culture to an uninfected one. Interestingly, NSC differentiation experiments demonstrated the influence of neural cell fate on production of PrPsc.
This novel cell culture model will provide new insights into the molecular basis of prion diseases and might pave the way to a new generation of diagnostic tools.
AD Sylvain Lehmann, Danielle Casanova, Ollivier Milhavet, CNRS UPR1142, Montpellier, France
SP englisch
PO Deutschland