title: The metabolism of glycosaminoglycans is impaired in prion diseases.
abstract: It is well established that the conversion of PrP(C) to PrP(Sc) is the key event in prion disease biology. In addition, several lines of evidence suggest that glycosaminoglycans (GAGs) and in particular heparan sulfate (HS) may play a role in the PrP(C) to PrP(Sc) conversion process. It has been proposed that PrP(Sc) accumulation in prion diseases may induce aberrant activation of lysosomal activity, which has been shown to result in neurodegeneration in a number of diseases, especially lysosomal storage disorders. Among such diseases, only the ones resulting from defects in GAGs degradation are accompanied by secretion of large amounts of GAG metabolites in urine. In this work, we show that GAGs are secreted in the urine of prion-infected animals and humans, and surprisingly, also in the urine of mice ablated for the PrP gene. We hypothesize that both the presence of PrP(Sc) or the absence of PrP(C) may alter the metabolism of GAGs.
authors.affiliation: Department of Neurology, The Agnes Ginges Center for Human Neurogenetics, Hadassah University Hospital, Jerusalem, 91120 Israel.
authors.forename: Tehila
authors.initials: T
authors.lastname: Mayer-Sonnenfeld
authors.forename: Marsha
authors.initials: M
authors.lastname: Zeigler
authors.forename: Michele
authors.initials: M
authors.lastname: Halimi
authors.forename: Yael
authors.initials: Y
authors.lastname: Dayan
authors.forename: Christian
authors.initials: C
authors.lastname: Herzog
authors.forename: Corinne I
authors.initials: CI
authors.lastname: Lasmezas
authors.forename: Ruth
authors.initials: R
authors.lastname: Gabizon
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D007562:Creutzfeldt-Jakob Syndrome / Q000235:genetics / Q000503:physiopathology / Q000652:urine; D006224:Cricetinae; D004195:Disease Models, Animal; D004789:Enzyme Activation / Q000235:genetics; D006025:Glycosaminoglycans / Q000652:urine*; D006596:Hexosaminidases / Q000378:metabolism; D006801:Humans; D008247:Lysosomes / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000378:metabolism; D018621:PrPC Proteins / Q000235:genetics / Q000378:metabolism*; D018620:PrPSc Proteins / Q000378:metabolism*; D017096:Prion Diseases / Q000235:genetics / Q000503:physiopathology / Q000652:urine*; D012608:Scrapie / Q000235:genetics / Q000503:physiopathology / Q000652:urine; D012756:Sheep; D015854:Up-Regulation / Q000235:genetics
chemical_list: D006025:Glycosaminoglycans; D018621:PrPC Proteins; D018620:PrPSc Proteins; D006596:Hexosaminidases