Dextran sulphate inhibits an association of prions with plasma membrane at the early phase of infection
| Autor: | Noriyuki Nishida, Naohiro Yamaguchi, Takujiro Homma, Daisuke Ishibashi, Hiroya Tange, Takayuki Fuse, Takehiro Nakagaki, Ryuichiro Atarashi |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
PrPSc Proteins Prions animal diseases Cell Hippocampus Endocytosis Prion Diseases Glycosaminoglycan Mice 03 medical and health sciences 0302 clinical medicine Neuroblastoma medicine Animals Lipid raft Chemistry General Neuroscience Cell Membrane Dextran Sulfate General Medicine medicine.disease nervous system diseases Cell biology 030104 developmental biology Membrane medicine.anatomical_structure nervous system Cell culture 030217 neurology & neurosurgery |
| Zdroj: | Neuroscience Research. 171:34-40 |
| ISSN: | 0168-0102 |
| DOI: | 10.1016/j.neures.2021.01.004 |
| Popis: | The defining characteristic of prion diseases is conversion of a cellular prion protein (PrPC) to an abnormal prion protein (PrPSc). The exogenous attachment of PrPSc to the surface of a target cell is critical for infection. However, the initial interaction of PrPSc with the cell surface is poorly characterized. In the current study, we specifically focused on the association of PrPSc with cells during the early phase of infection, using an acute infection model. First, we treated mouse neuroblastoma N2a-58 cells with prion strain 22 L-infected brain homogenates and revealed that PrPSc was associated with membrane fractions within three hours, a short exposure time. These results were also observed in PrPC-deficient hippocampus cell lines. We also demonstrate here that PrPSc from 22 L-infected brain homogenates was associated with lipid rafts during the early phase of infection. Furthermore, we revealed that DS500, a glycosaminoglycan mimetic, inhibited both the attachment of PrPSc to membrane fractions and subsequent prion transmission, suggesting that the early association of prions with cell surface is important for prion infection. |
| Databáze: | OpenAIRE |
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