title: Cathepsin B and L are involved in degradation of prions in GT1-1 neuronal cells.
abstract: In scrapie-infected cells, the abnormal isoform of the prion protein, PrP(Sc), accumulates in endosomes/lysosomes. In this study, the involvement of two lysosomal proteases, cathepsin B and L, in cellular processing of PrP(Sc) was analyzed in immortalized neuronal gonadotropin-releasing hormone cells (GT1-1) infected with scrapie. Treatment with inhibitors of either cathepsin B or L resulted in accumulation of PrP(Sc). Such an increased accumulation also occurred when the activities of both cathepsins were inhibited using RNA interference. We conclude that cathepsin B and L are involved in the degradation of PrP(Sc) in scrapie-infected GT1-1 cells and that they can compensate for each other's functions. This study shows that specific proteases, abundantly present in neurons, have the capacity to degrade PrP(Sc).
authors.affiliation: Department of Neuroscience B2:5, Retzius väg 8, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
authors.forename: Katarina M
authors.initials: KM
authors.lastname: Luhr
authors.forename: Elin K
authors.initials: EK
authors.lastname: Nordström
authors.forename: Peter
authors.initials: P
authors.lastname: Löw
authors.forename: Krister
authors.initials: K
authors.lastname: Kristensson
mesh_terms: D000818:Animals; D015153:Blotting, Western / Q000379:methods; D002401:Cathepsin B / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D056668:Cathepsin L; D002403:Cathepsins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D003546:Cysteine Endopeptidases; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism; D007031:Hypothalamus; D051379:Mice; D009474:Neurons / Q000378:metabolism* / Q000821:virology; D018620:PrPSc Proteins / Q000378:metabolism; D011328:Prions / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D034741:RNA, Small Interfering / Q000378:metabolism / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D014162:Transfection / Q000379:methods
chemical_list: D018620:PrPSc Proteins; D011328:Prions; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D007987:Gonadotropin-Releasing Hormone; D002403:Cathepsins; D003546:Cysteine Endopeptidases; D002401:Cathepsin B; D056668:Cathepsin L; C534278:Ctsl protein, mouse