NR AXQF
AU Kovacs,G.G.; Gelpi,E.; Ströbel,T.; Kopitar-Jerala,N.; Turk,B.; Budka,H.
TI Pathogenetic Role of Lysosomal Cathepsins in Human Prion Disease
QU International Conference - Prion 2007 (26.-28.9.2007) Edinburgh International Conference Centre, Edinburgh, Scotland, UK - Book of Abstracts: Pathology and Pathogenesis P03.15
IA http://www.prion2007.com/pdf/Prion Book of Abstracts.pdf
PT Konferenz-Poster
AB
Ultrastructural, immunohistochemical, enzyme activity, as well as gene expression studies suggest the endosomal-lysosomal system to play an important role in the pathogenesis of prion diseases. Cathepsins are lysosomal enzymes with distinct physiological functions. A C-to-T polymorphism in exon 2 of the cathepsin D gene associates with altered enzymatic activity. First, we evaluated the immunohistochemical expression of cathepsins B, D, F, H, and L in sporadic Creutzfeldt-Jakob disease (sCJD) brain sections. Anti-cathepsin B, D, F, and H immunostaining revealed immunoreactive dots in neurons. Certain cathepsins appear in astro- and microglial cells in prion disease and not in controls. The volume density of lysosomes indicated by anti-cathepsin D immunoreactivity correlates with tissue pathology. Disease-associated prion protein (PrPTSE) focally co-localizes with cathepsin D. Second, we evaluated the C224T cathepsin D polymorphism, as well as the PRNP polymorphism at codon 129 and apolipoprotein E (apoE) isotypes in 66 sCJD and 98 control cases. Preliminary results indicate that the duration of illness in C224T sCJD patients is shorter than in C224C CJD patients. In addition, there are certain constellations that include apoE isotypes and PRNP codon 129, which seem to associate with a poor prognosis. In sum, (1) neuronal cathepsin D immunoreactivity associates with tissue pathology and PrPTSE, and (2) the C224T polymorphism of its gene may influence disease course in sCJD. This further corroborates an important pathogenetic role of the endosomal-lysosomal system in prion diseases.
Supported by the EU FP6 Network of Excellence, NeuroPrion.
AD G.G. Kovacs, E. Gelpi, T. Ströbel, H. Budka, Medical University of Vienna, Institute of Neurology, Austria; N. Kopitar-Jerala, B. Turk, Jozef Stefan Institute, Biochemistry, Molecular and Structural Biology, Slovenia
SP englisch
PO Schottland