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

• Published in: The American journal of pathology Vol. 184; no. 12; pp. 3299 - 3307
• Main Authors: Choi, Young Pyo, Head, Mark W, Ironside, James W, Priola, Suzette A
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.12.2014; American Society for Investigative Pathology
• Subjects: Animals; Astrocytes - cytology; Astrocytes - metabolism; Brain - metabolism; Brain - pathology; Creutzfeldt-Jakob Syndrome - metabolism; Endopeptidase K - chemistry; Epitopes - chemistry; Fibroblasts - metabolism; Humans; Immunoprecipitation; Mice; Microscopy, Fluorescence; Pathology; Peptide Hydrolases - chemistry; Phosphotungstic Acid - chemistry; Prion Diseases - metabolism; Prions - metabolism; PrPC Proteins - metabolism; PrPSc Proteins - metabolism; Regular
• ISSN: 0002-9440; 1525-2191
• DOI: 10.1016/j.ajpath.2014.08.005

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 (PrPSc ) of the host prion protein. In sporadic Creutzfeldt-Jakob disease, disease-associated PrPSc is present not only as an aggregated, protease-resistant form but also as an aggregated protease-sensitive form (sPrPSc ). Although evidence suggests that sPrPSc 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 PrPSc . Furthermore, the cell does not appear to distinguish between sPrPSc and protease-resistant PrPSc , suggesting that sPrPSc could contribute to prion infection.