| Autor: |
Elisabet Ihse, Hodaka Yamakado, Xander M. van Wijk, Roger Lawrence, Jeffrey D. Esko, Eliezer Masliah |
| Jazyk: |
angličtina |
| Rok vydání: |
2017 |
| Předmět: |
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| Zdroj: |
Scientific Reports, Vol 7, Iss 1, Pp 1-10 (2017) |
| Druh dokumentu: |
article |
| ISSN: |
2045-2322 |
| DOI: |
10.1038/s41598-017-08720-5 |
| Popis: |
Abstract Amyloid aggregates found in the brain of patients with neurodegenerative diseases, including Alzheimer’s and Parkinson’s disease, are thought to spread to increasingly larger areas of the brain through a prion-like seeding mechanism. Not much is known about which cell surface receptors may be involved in the cell-to-cell transfer, but proteoglycans are of interest due to their well-known propensity to interact with amyloid aggregates. In this study, we investigated the involvement of plasma membrane-bound heparan and chondroitin sulfate proteoglycans in cellular uptake of aggregates consisting of α-synuclein, a protein forming amyloid aggregates in Parkinson’s disease. We show, using a pH-sensitive probe, that internalization of α-synuclein amyloid fibrils in neuroblastoma cells is dependent on heparan sulfate, whereas internalization of smaller non-amyloid oligomers is not. We also show that α-synuclein fibril uptake in an oligodendrocyte-like cell line is equally dependent on heparan sulfate, while astrocyte- and microglia-like cell lines have other means to internalize the fibrils. In addition, we analyzed the interaction between the α-synuclein amyloid fibrils and heparan sulfate and show that overall sulfation of the heparan sulfate chains is more important than sulfation at particular sites along the chains. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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