Cellular internalization of alpha-synuclein aggregates by cell surface heparan sulfate depends on aggregate conformation and cell type

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...

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Autores principales:	Elisabet Ihse, Hodaka Yamakado, Xander M. van Wijk, Roger Lawrence, Jeffrey D. Esko, Eliezer Masliah
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3816af4f87464e5997d5687d0cff4d29
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spelling	oai:doaj.org-article:3816af4f87464e5997d5687d0cff4d292021-12-02T15:05:20ZCellular internalization of alpha-synuclein aggregates by cell surface heparan sulfate depends on aggregate conformation and cell type10.1038/s41598-017-08720-52045-2322https://doaj.org/article/3816af4f87464e5997d5687d0cff4d292017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-08720-5https://doaj.org/toc/2045-2322Abstract 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.Elisabet IhseHodaka YamakadoXander M. van WijkRoger LawrenceJeffrey D. EskoEliezer MasliahNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Elisabet Ihse Hodaka Yamakado Xander M. van Wijk Roger Lawrence Jeffrey D. Esko Eliezer Masliah Cellular internalization of alpha-synuclein aggregates by cell surface heparan sulfate depends on aggregate conformation and cell type
description	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.
format	article
author	Elisabet Ihse Hodaka Yamakado Xander M. van Wijk Roger Lawrence Jeffrey D. Esko Eliezer Masliah
author_facet	Elisabet Ihse Hodaka Yamakado Xander M. van Wijk Roger Lawrence Jeffrey D. Esko Eliezer Masliah
author_sort	Elisabet Ihse
title	Cellular internalization of alpha-synuclein aggregates by cell surface heparan sulfate depends on aggregate conformation and cell type
title_short	Cellular internalization of alpha-synuclein aggregates by cell surface heparan sulfate depends on aggregate conformation and cell type
title_full	Cellular internalization of alpha-synuclein aggregates by cell surface heparan sulfate depends on aggregate conformation and cell type
title_fullStr	Cellular internalization of alpha-synuclein aggregates by cell surface heparan sulfate depends on aggregate conformation and cell type
title_full_unstemmed	Cellular internalization of alpha-synuclein aggregates by cell surface heparan sulfate depends on aggregate conformation and cell type
title_sort	cellular internalization of alpha-synuclein aggregates by cell surface heparan sulfate depends on aggregate conformation and cell type
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/3816af4f87464e5997d5687d0cff4d29
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Cellular internalization of alpha-synuclein aggregates by cell surface heparan sulfate depends on aggregate conformation and cell type

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