Identification of an Intracellular Site of Prion Conversion

Prion diseases are fatal, neurodegenerative disorders in humans and animals and are characterized by the accumulation of an abnormally folded isoform of the cellular prion protein (PrPC), denoted PrPSc, which represents the major component of infectious scrapie prions. Characterization of the mechanism of conversion of PrPC into PrPSc and identification of the intracellular site where it occurs are among the most important questions in prion biology. Despite numerous efforts, both of these questions remain unsolved. We have quantitatively analyzed the distribution of PrPC and PrPSc and measured PrPSc levels in different infected neuronal cell lines in which protein trafficking has been selectively impaired. Our data exclude roles for both early and late endosomes and identify the endosomal recycling compartment as the likely site of prion conversion. These findings represent a fundamental step towards understanding the cellular mechanism of prion conversion and will allow the development of new therapeutic approaches for prion diseases

Total and differential cross sections of eta-production in proton-deuteron fusion for excess energies between Q(eta)=13 MeV and Q(eta)=81 MeV

New data on both total and differential cross sections of the production of eta mesons in proton-deuteron fusion to He-3 eta in the excess energy region 13.6 MeV <= Q(eta) <= 80.9 MeV are presented. These data have been obtained with the WASA-at-COSY detector setup located at the Forschungszentrum Julich, using a proton beam at 15 different beam momenta between p(p) = 1.60 GeV/c and p(p) = 1.74 GeV/c. While significant structure of the total cross section is observed in the energy region 20 MeV less than or similar to Q(eta) less than or similar to 60 MeV, a previously reported sharp variation around Q(eta) approximate to 50 MeV cannot be confirmed. Angular distributions show the typical forward- peaking that was noted earlier. For the first time, it is possible to study the development of these angular distributions with rising excess energy over a wide interval. (c) 2018 The Author. Published by Elsevier B.V