Uptake and Degradation of Protease-Sensitive and -Resistant Forms of Abnormal Human Prion Protein Aggregates by Human Astrocytes

Young Pyo Choi, Mark W Head, James W Ironside, Suzette A Priola

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)3299-3307
Number of pages9
JournalAmerican Journal of Pathology
Volume184
Issue number12
DOIs
Publication statusPublished - Dec 2014

Keywords

  • CREUTZFELDT-JAKOB-DISEASE
  • POLYSACCHARIDE SCAFFOLD
  • DENDRITIC CELLS
  • NEURONAL CELLS
  • SCRAPIE
  • PRPSC
  • INFECTION
  • CONFORMERS
  • CLEARANCE
  • DIAGNOSIS

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