NR AWIE
AU Kovacs,G.G.; Karapetyan,Y.; Gelpi,E.; Ricken,G.; Laszlo,L.; Budka,H.
TI The orchestra of pathogenetic events in human prion disease: who is the conductor?
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-30
PT Konferenz-Poster
AB In sporadic Creutzfeldt-Jakob disease (CJD), distribution of affected brain regions is distinct between prion protein (PrP) genotypes at the polymorphic codon 129. Neuropathological studies have revealed different pathways of neuronal damage, like oxidative stress, apoptosis, complement activation, and involvement of the endosomal-lysosomal system. It is not clear which cell death pathways are important and whether neuronal death occurs randomly or in common vulnerable areas. Here we evaluated immunohistochemically the distribution of components related to different stages of cell death (BAX, PARP, C-Jun, Caspase 3 and 9, NfKB, BCL-2) in 30 well defined anatomical area in sporadic CJD subtypes. We performed double immunolabelling of the aforementioned and other components suggested to be important in disease pathogenesis, like the membrane attack complex (MAC) of the complement pathway, nitrotyrosine representing oxidative stress, cathepsin D lysosomal enzyme, and stress related protein Hsp72, using laser scanning confocal microscope. We observed variable distribution of cell-death related proteins within and between CJD subgroups. However in CJD subgroups we noted shared involvement of certain anatomical areas proposing common vulnerable areas. While upregulation and altered cellular distribution of cathepsin D correlates with caspase mediated cell death, MAC is controlled by complement regulatory proteins, and deposits only in severely affected areas. Furthermore, vulnerability of neurons depends on the capability of expressing cellular PrP preserving and cytoprotective proteins like Hsp72. In sum, neither investigated components proved to have an exclusive pathogenetic role in CJD, suggesting orchestral players who act without a conductor, in both con- and dissonance.
AD G.G. Kovacs: Institute of Neurology, Medical University of Vienna, and Austrian Reference Center for Human Prion Diseases, Vienna, Austria and National Institute of Psychiatry and Neurology, and Hungarian Reference Center for Human Prion diseases, Budapest, Hungary; Y. Karapetyan, E. Gelpi, G. Ricken, H. Budka: Institute of Neurology, Medical University of Vienna, and Austrian Reference Center for Human Prion Diseases, Vienna, Austria; L. Laszlo: Dept. of Anatomy, Cell and Developmental Biology, Eötvös University, Budapest, Hungary
SP englisch
PO Italien