Probing molecular mechanisms of neurodegenerative ageing in prion ablated mice
Funded by BBSRC
Associated scientist: Dr. Steve Banner and Dr Andrew C. Gill
It is not clear whether characteristic TSE neuronal loss is caused by the build up of PrPSc amyloidogenic protein directly, or whether pathology results from loss of PrPC from the cell surface. This uncertainty is largely because the normal function of PrPC is currently unknown; mice in which the gene encoding PrP has been knocked out appear to develop normally although have subtle phenotypic defects in various physiological functions. We have preliminary microarray evidence for loss of specific cell types from the brains of aged PrP knock-out mice which implies that it may be loss of function of PrPC that is the root cause of pathology in TSE diseases. Our results suggest that PrPC is an important neuroprotective molecule during ageing that helps prevent neuronal damage by reactive oxygen species. This project is following up our initial work with targeted microarray (Dr Alan Clarke, University of Cardiff), proteomics and immunohistopathological experiments. Our proteomic work involves 2-dimensional gel separations of proteins dervied from the brains of aged knockout mice and age-matched controls. We are also studying proteomic differences in other PrP transgenic mice as a means to define PrPC function.
More details: please contact Andrew C. Gill