NR AOQV
AU Budka,H.
TI Central Pathogenesis of Prion Diseases
QU International Conference - Prion diseases: from basic research to intervention concepts - TSE-Forum, 08.10.-10.10.2003, Gasteig, München - Oral sessions OS-18
PT Konferenz-Vortrag
AB In contrast with the elucidation of peripheral TSE pathogenesis by elegant modelling, much is unknown about the central pathogenesis of TSEs. However, some progress has recently been made. The severity of tissue damage does not always correlate with the amount and time course of prion protein (PrP) deposition in the diseased brain. While neuronal damage appears as functionally most important event, this is not evenly distributed between brain regions and cases. We found severe, early and selective neuronal vulnerability of the parvalbumin-decorated subset of inhibitory GABAergic neurons both in human and experimental TSEs. Moreover, prominent neuronal labelling for oxidative stress products, again both in human and experimental TSEs, suggests oxidative stress as important pathogenetic event, similarly to other neurodegenerative disorders including Alzheimer's disease (AD). Most recently, we found complement activation and the membrane attack complex in human TSE brains, suggesting complement-mediated cell lysis, again similarly to other neurodegenerative disorders including AD. Some tiny granular periaxonal PrP deposits, seen in experimental and rarely human TSEs, might relate with the postulated prion passage along peripheral nerves. However, we recently found disease-associated PrP in cell within the walls of intra- and extracranial vessels, suggesting a potential transport of PrP/infectivity by mobile cells. Abundance of PrPsc in muscle tissue of a CJD patient who also suffered from inclusion body myositis suggests upregulation of PrPc (such as in IBM) as important factor for PrPsc deposition in tissues. (This review is supported by the EU QoL project PRIONET)
AD Herbert Budka, Institute of Neurology, University of Vienna, Austria
SP englisch
PO Deutschland