NR ALFM
AU Stumpf,M.P.; Krakauer,D.C.
TI Mapping the parameters of prion-induced neuropathology
QU Proceedings of the National Academy of Sciences of the United States of America 2000 Sep 12; 97(19): 10573-7
PT journal article
AB We present a theoretical framework that enables us to dissect out the parametric dependencies of the pathogenesis of prion diseases. We are able to determine the influence of both host-dependent factors (connectivity, cell density, protein synthesis rate, and cell death) and strain-dependent factors (cell tropism, virulence, and replication rate). We use a model based on a linked system of differential equations on a lattice to explore how the regional distribution of central nervous system pathology in Creutzfeldt-Jakob disease, Gerstmann-Sträussler-Scheinker syndrome, and fatal familial insomnia relates to each of these factors. The model then is used to make qualitative predictions about the pathology for two possible hypothetical triggers of neuronal loss in prion diseases. Pathological progression in overexpressing mouse models has been shown to depend on the site of initial infection. The model allows us to compare the pathologies resulting from different inoculation routes.
MH Apoptosis; Prion Diseases/pathology/*virology; Prions/metabolism/*pathogenicity; Support, Non-U.S. Gov't; Tropism
AD The Wellcome Trust Centre for the Epidemiology of Infectious Disease, Department of Zoology, South Parks Road, Oxford OX1 3PS, United Kingdom.
SP englisch
PO USA