RESUMO
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.
Assuntos
Encéfalo/metabolismo , Glicosaminoglicanos/urina , Proteínas PrPC/metabolismo , Proteínas PrPSc/metabolismo , Doenças Priônicas/urina , Animais , Encéfalo/patologia , Encéfalo/fisiopatologia , Síndrome de Creutzfeldt-Jakob/genética , Síndrome de Creutzfeldt-Jakob/fisiopatologia , Síndrome de Creutzfeldt-Jakob/urina , Cricetinae , Modelos Animais de Doenças , Ativação Enzimática/genética , Hexosaminidases/metabolismo , Humanos , Lisossomos/metabolismo , Masculino , Camundongos , Camundongos Knockout , Neurônios/metabolismo , Proteínas PrPC/genética , Doenças Priônicas/genética , Doenças Priônicas/fisiopatologia , Scrapie/genética , Scrapie/fisiopatologia , Scrapie/urina , Ovinos , Regulação para Cima/genéticaRESUMO
The necessity of a non-invasive in-vivo test for prion diseases has become more apparent since the transmission of vCJD from the blood of a healthy individual incubating the disease. Here we show that prion urine comprises an array of protease resistant peptides, among them light chain immunoglobulin (LC). This was observed by sequencing gel bands comprising hamster urine samples, as well as by immunoblotting of similar samples with anti mouse IgG reagents for hamster samples, or with anti human IgG reagents for human samples. Our result suggests that urine samples from CJD patients can be identified by the presence of protease resistant proteins such as LC.
