NR AWKL
AU Moleres,F.J.; Castle,M.; Gambetti,P.; Petersen,R.B.; Velayos,J.L.
TI Expression of the cellular prion protein in the rat brain and characterization of animal models of fatal familial insomnia
QU International Conference - Prion 2006: Strategies, advances and trends towards protection of society - 3.10.-6.10.2006, Torino, Italy, Lingotto Conference Centre - Poster sessions PA-40
PT Konferenz-Poster
AB The cellular prion protein (PrPc) is a membrane-bound glycoprotein mainly present in the central nervous system of mammals. Prions (PrPsc) are conformationally-altered isoforms of PrPc that are responsible for transmissible spongiform encephalopathies (TSE), a group of neurodegenerative diseases affecting both humans and animals. As the presence of PrPc is necessary for the establishment and further evolution of these pathologies, we have mapped its regional distribution in the rat brain and studied the chemical nature of these neurons. We have also generated a line of transgenic mice (Tg) that mimics some of the most relevant biochemical features of fatal familial insomnia (FFI), a human TSE where the damage is primarily confined to the thalamus. Additionally, we have injected neuronal tracers into the rat thalamus in order to explain the pathogenic mechanism leading to FFI. The ubiquitous distribution of PrPc throughout the rat brain, especially in areas that send projections to the thalamus, together with its neurochemical partners and the connectivity of the rat thalamus, suggests that there is a retrograde transport of prions in FFI. The characterization of Tg(FFI) validates it as a good model for FFI and reveals that our observations in rat can be further extrapolated to human subjects. With the combination of all these approaches, and based on this retrograde transport, we are now able to successfully explain some characteristic pathogenic features observed in FFI patients and to explain the selective vulnerability of particular subsets of cells in animal and human TSE. Supported by PIUNA and BMH4-CT96-856 (to JLV) and by NIH grant AG14359; CDC Grant CCU 515004 and the Britton Fund. (to PG). FJM is supported by a FPU grant 2003-5033.
AD F.J. Moleres: Department of Anatomy, Universidad de Navarra, Pamplona, Spain, and Institute of Pathology, Case Western Reserve University, Cleveland, OH, USA; M. Castle, J.L. Velayos: Department of Anatomy, Universidad de Navarra, Pamplona, Spain; P. Gambetti, R.B. Petersen: Institute of Pathology, Case Western Reserve University, Cleveland, OH, USA
SP englisch
PO Italien