NR AWNX
AU Slivarichova,D.; Mitrova,E.; Ursinyova,M.; Masanova,V.
TI Exogenous risk factor of CJD in regions with its increased occurrence in Slovakia
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 RA-12
PT Konferenz-Poster
AB Slovakia is characterized by unique proportion of genetic CJD (gCJD) with E200K mutation. Since the penetrance of the mutation is incomplete (59%) probably also other factors may influence the disease course.The precursor of the prion (PrPsc) is a normal cellular prion protein (PrPc), which under physiological conditions binds copper (Cu) and this linkage regulates the resistance of cells to the oxidation stress and apoptosis. Experimentaly was demonstrated that in a case of Cu deficiency other metals (mainly manganese) can replace Cu, forming misfolded metallo-glycoprotein with a similar physical-chemical properties as PrPsc. The role of described changes in the pathogenesis of prion diseases is not clear. The majority of Slovak gCJD originate from nothern and southern parts of Central Slovakia. In both regions are factories (ferromanganese and glass) - potentionall sources of atmospheric Mn contamination. Previously we demonstrated significant Mn/Cu disbalance in the soil and food chain in the Slovak CJD clusters area. Our objective was to determine Mn, Cu levels in the CNS of CJD patients as a pilot study for further investigation of Mn/Cu disbalance as a possible cofactor in the development clinical manifestation of CJD. Mn and Cu concentrations in 24 CNS samples (8 gCJD, 8 sporadic (sCJD), 8 controls without neurol.signs) were determined by flame AAS. Analyses demonstrate i) mean Mn level 0,6088mg/kg for gCJD, 0,3675mg/kg for sCJD, 0,3000mg/kg for controls, the difference between genetic and control groups was significant (p=0,003) ii), mean Cu status in gCJD 5,475mg/kg, sCJD 4,738mg/kg, controls 4,700mg/kg; iii) mean Mn/Cu ratios in gCJD 11,4338, sCJD 7,9738 and controls 6,4888. Mn/Cu ratios in our genetic group show strong disbalance of metal ions in CNS in comparison to those of control group. Results warrant further studies, whether the observed coincidence of endogenous (genetic) risk and a possible environment. risk factor may be involved in the ethiopathogenesis of gCJD and to contribute to the focal CJD accumulation in Slovakia. Work was supported by Science and Technology Assistance Agency, contract No. APVT-21-019004.
AD D. Slivarichová, E. Mitrová: Department of prion diseases, Slovak Medical University, Limbová 12, 83301 Bratislava, Slovakia; M. Ursínyová, V. Masánová: Laboratory of toxic and essential elements, Slovak Medical University, Limbová 12, 83301 Bratislava, Slovakia. E-mail: dana.slivarichova@szu.sk
SP englisch
PO Italien