NR AXZO
AU Zanusso,G.; Commoy,E.; Fasoli,E.; Fiorini,M.; Lescoutra,N.; Ruchoux,M.M.; Casalone,C.; Caramelli,M.; Ferrari,S.; Lasmezas,C.; Deslys,J.P.; Monaco,S.
TI BASE Transmitted to Primates and MV2 sCJD Subtype Share PrP27-30 and PrPsc C-terminal Truncated Fragments
QU International Conference - Prion 2007 (26.-28.9.2007) Edinburgh International Conference Centre, Edinburgh, Scotland, UK - Book of Abstracts: Oral Abstracts FC5.5.1
IA http://www.prion2007.com/pdf/Prion Book of Abstracts.pdf
PT Konferenz-Vortrag
AB
The etiology of sporadic Creutzfeldt-Jakob disease (sCJD), the most frequent human prion disease, remains still unknown. The marked disease phenotype heterogeneity observed in sCJD is thought to be influenced by the type of proteinase K-resistant prion protein, or PrPsc (type 1 or type 2 according to the electrophoretic mobility of the unglycosylated backbone), and by the host polymorphic Methionine/Valine (M/V) codon 129 of the PRNP. By using a two-dimensional gel electrophoresis (2D-PAGE) and imunoblotting we previously showed that in sCJD, in addition to the PrPsc type, distinct PrPsc C-terminal truncated fragments (CTFs) correlated with different sCJD subtypes. Based on the combination of CTFs and PrPsc type, we distinguished three PrPsc patterns: (i) the first was observed in sCJD with PrPsc type 1 of all genotypes,;
(ii) the second was found in M/M-2 (cortical form); (iii) the third in amyloidogenic M/V2 and V/V-2 subtypes (Zanusso et al., JBC 2004) . Recently, we showed that sCJD subtype M/V-2 shared molecular and pathological features with an atypical form of BSE, named BASE, thus suggesting a potential link between the two conditions. This connection was further confirmed after 2D-PAGE analysis, which showed an identical PrPsc signature, including the biochemical pattern of CTFs. To pursue this issue, we obtained brain homogenates from Cynomolgus macaques intracerebrally inoculated with brain homogenates from BASE. Samples were separated by using a twodimensional electrophoresis (2D-PAGE) followed by immunoblotting. We here show that the PrPsc pattern obtained in infected primates is identical to BASE and sCJD MV-2 subtype. These data strongly support the link, or at least a common ancestry, between a sCJD subtype and BASE. This work was supported by Neuroprion (FOOD-CT-2004-506579)
AD G. Zanusso, University of Verona, of Neurological and Visual Sciences, Italy; E. Commoy, CEA, IMETI/SEPIA, France; E. Fasoli, M. Fiorini, S. Ferrari, S. Monaco, University of Verona, Neurological and Visual Sciences, Italy; N. Lescoutra, M.M. Ruchoux, J.-P. Deslys, IMETI/SEPIA, France; C. Casalone, M. Caramelli, IZSPLVA, Italy; C. Lasmezas, The Scripps Research Insitute, USA
SP englisch
PO Schottland