title: Up-regulation of cathepsin B and cathepsin L activities in scrapie-infected mouse Neuro2a cells.
abstract: Prion diseases are characterized by the accumulation of an abnormal, proteinase K-resistant isoform of the prion protein, PrP(Sc), which is generated by a post-translational conversion of the protease-sensitive normal cell-surface glycoprotein PrP(c) involving major conformational changes. The conversion is thought to occur at the plasma membrane or along the endocytic pathway towards the lysosome. PrP(Sc) aggregates have been found to accumulate in secondary lysosomes. In our study, the activities of two major lysosomal cysteine proteases, cathepsins B and L, were found to be significantly increased in scrapie-infected Neuro2a cells compared with uninfected cells using biochemical and cytochemical methods. We hypothesize that lysosomal proteases may be involved in a 'second autocatalytic loop' of PrP(Sc) formation, acting in concert with the well-known autocatalytic enhancement of PrP conversion in the presence of PrP(Sc).
authors.affiliation: Abteilung Tumorvirologie, Deutsches Krebsforschungszentrum, Heidelberg, Germany.|Department of Gerontology, Institute for Ageing and Health, University of Newcastle upon Tyne, Newcastle upon Tyne, UK.
authors.forename: Yonghua
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Arbeitsgruppe Biomedizinische Strukturforschung, Deutsches Krebsforschungszentrum, Heidelberg, Germany.
authors.forename: Eberhard
authors.initials: E
authors.lastname: Spiess
authors.affiliation: Arbeitsgruppe Biomedizinische Strukturforschung, Deutsches Krebsforschungszentrum, Heidelberg, Germany.
authors.forename: Martin H
authors.initials: MH
authors.lastname: Groschup
authors.affiliation: Abteilung Tumorvirologie, Deutsches Krebsforschungszentrum, Heidelberg, Germany.|Department of Gerontology, Institute for Ageing and Health, University of Newcastle upon Tyne, Newcastle upon Tyne, UK.
authors.forename: Alexander
authors.initials: A
authors.lastname: Bürkle
mesh_terms: D000818:Animals; D002401:Cathepsin B / Q000378:metabolism*; D056668:Cathepsin L; D002403:Cathepsins / Q000378:metabolism*; D003546:Cysteine Endopeptidases; D051379:Mice; D009447:Neuroblastoma; D009474:Neurons / Q000378:metabolism*; D018620:PrPSc Proteins / Q000472:pathogenicity*; D012608:Scrapie / Q000378:metabolism; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
chemical_list: D018620:PrPSc Proteins; D002403:Cathepsins; D003546:Cysteine Endopeptidases; D002401:Cathepsin B; D056668:Cathepsin L; C534278:Ctsl protein, mouse