NR ASAS
AU anonym
TI Pathogenesis of transmissible spongiform encephalopathies - summary of ongoing research
QU UK Institute of Animal Health
IA http://www.iah.bbsrc.ac.uk/institut/public/3wplann.htm#twelve (nicht mehr vorhanden)
PT Research Report
VT
Diseases such as scrapie, bovine spongiform encephalopathy and Creutzfeldt-Jakob disease are characterised by long incubation times, progressive neuronal cell degeneration, vacuolation in discrete regions of the CNS and the accumulation of the amyloid PrPsc. There is no detectable immune response although the cells of the immune system are involved in the infection.
There are several strains of infectious agent but there is a need to establish the extent and significance of strain variation in natural infections, how these strains are generated and selected and the importance of strains in determining the "species barrier".
Natural infections may be initiated via a peripheral route; work on the peripheral pathogenesis will determine the course of replication of the infectious agent and accumulation of PrPsc in cells of peripheral organs. The identity of the peripheral cells involved in the species barrier and the role of the Sinc or Sip and PrP genes have to be established with PrP-null, transgenic and SCID mice providing important new tools for this research. A major goal will be to identify the staging of occurrence and cell location of diagnostic PrP.
While peripheral processes are important in the development of the disease, the events in the CNS ultimately give rise to clinical signs of disease. Studies of CNS pathogenesis involve measuring in different models of scrapie the temporal and spatial relationships between various pathological indicators of infection-PrPsc, amyloidosis, microgliosis, vacuolation, ubiquitination, and neuronal degeneration and loss. This will lead to an understanding of the cellular and molecular mechanisms of uptake, processing and transport of infectivity through the CNS, neuron-specific targeting by different scrapie strains and the role of the Sinc and Sip genes in scrapie pathogenesis.
The programme also includes work to identify the natural modes of transmission of scrapie in sheep and the bizarre resistance of scrapie-like agents to all forms of inactivation remains a major scientific and practical challenge.
SP englisch
OR Prion-Krankheiten 9