Uptake and degradation of protease-sensitive and -resistant forms of abnormal human prion protein aggregates by human astrocytes.
Am J Pathol
; 184(12): 3299-307, 2014 Dec.
Article
em En
| MEDLINE
| ID: mdl-25280631
ABSTRACT
Sporadic Creutzfeldt-Jakob disease is the most common of the human prion diseases, a group of rare, transmissible, and fatal neurologic diseases associated with the accumulation of an abnormal form (PrP(Sc)) of the host prion protein. In sporadic Creutzfeldt-Jakob disease, disease-associated PrP(Sc) is present not only as an aggregated, protease-resistant form but also as an aggregated protease-sensitive form (sPrP(Sc)). Although evidence suggests that sPrP(Sc) may play a role in prion pathogenesis, little is known about how it interacts with cells during prion infection. Here, we show that protease-sensitive abnormal PrP aggregates derived from patients with sporadic Creutzfeldt-Jakob disease are taken up and degraded by immortalized human astrocytes similarly to abnormal PrP aggregates that are resistant to proteases. Our data suggest that relative proteinase K resistance does not significantly influence the astrocyte's ability to degrade PrP(Sc). Furthermore, the cell does not appear to distinguish between sPrP(Sc) and protease-resistant PrP(Sc), suggesting that sPrP(Sc) could contribute to prion infection.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Peptídeo Hidrolases
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Encéfalo
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Príons
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Astrócitos
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Síndrome de Creutzfeldt-Jakob
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Proteínas PrPC
Tipo de estudo:
Diagnostic_studies
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article