NR AOWG
AU Mallucci,G.R.; Dickinson,A.; Linehan,J.; Brandner,S.; Collinge,J.
TI Depletion of neuronal prion protein (PrP) during prion infection prevents disease and reverses spongiform pathology
QU International Conference - Prion diseases: from basic research to intervention concepts - TSE-Forum, 08.10.-10.10.2003, Gasteig, München - Oral sessions OS-23
PT Konferenz-Vortrag
AB The mechanisms involved in prion neurotoxicity are unclear and therapies preventing accumulation of PrPsc, the disease-associated form of PrP, do not significantly prolong survival in prion-infected mice. We depleted neuronal PrPc in mice with neuroinvasive prion infection and established neuropathology, preventing its continued conversion to PrPsc. We found that early spongiform change was reversed as a result of this depletion and that subsequently neuronal loss and progression to clinical disease were prevented in these animals 4 x beyond the normal incubation period. This occurred despite the accumulation of extra-neuronal PrPsc to levels seen in terminally ill wild type animals. We conclude that the propagation of non-neuronal PrPsc is not pathogenic, but that arresting the continued conversion of PrPc to PrPsc specifically within neurons during prion infection prevents prion neurotoxicity. These results have important implications for therapeutic strategies in prion disease.
AD Giovanna Mallucci, Andrew Dickinson, Jackie Linehan, Sebastian Brandner, John Collinge, MRC PRION Unit, London, UK
SP englisch
PO Deutschland