NR ATOV
AU Unterberger,U.; Hoeftberger,R.; Gelpi,E.; Flicker,H.; Budka,H.; Voigtlaender,T.
TI Prion Diseases Differ from Alzheimer's Disease with Respect to the Activation of ER Stress Mechanisms
QU International Conference - Prion 2005: Between fundamentals and society's needs - 19.10.-21.10.2005, Congress Center Düsseldorf - Poster Session: Pathogenesis PATH-06
PT Konferenz-Poster
AB Prion diseases and Alzheimer's disease share a variety of clinical and neuropathological features - in particular progressive dementia, extraneuronal accumulation of abnormal proteins, and pronounced neuronal loss -, as well as presumably pathogenic mechanisms, like generation of oxidative stress molecules and complement activation. Recently, it has been suggested that neuronal death in Alzheimer's disease may have its origin in the endoplasmic reticulum (ER). Cellular stress conditions can interfere with protein folding and subsequently cause accumulation of unfolded or misfolded proteins in the ER lumen. The ER responds to this by the activation of adaptive pathways, which are, taken together, termed the unfolded protein response (UPR). We demonstrate that the UPR transducer PERK, which launches the most immediate response to ER stress, namely the transient attenuation of mRNA translation, and the downstream effector of PERK, eIF2alpha, are activated in neurons of patients with Alzheimer's disease, whereas neither in sporadic, nor in infectiously acquired or inherited human prion diseases the phosphorylated forms of PERK and eIF2alpha could be detected by immunohistochemistry. In the brains of scrapie affected mice, only a very faint expression of activated PERK was visible. The distribution of phosphorylated UPR molecules in Alzheimer's disease correlated with pathologically phosphorylated tau, as well as with activation of the cell stress kinase PKR, and of p38 MAP kinase. The lack of a prominent activation of the PERK-eIF2alpha pathway suggests that, in contrast to Alzheimer's disease, ER stress does not play a crucial role in neuronal death in prion diseases.
AD U.Unterberger, R.Hoeftberger, E.Gelpi, H.Flicker, H.Budka, T.Voigtlaender, Institute of Neurology, Medical University of Vienna, Austria
SP englisch
PO Deutschland