α-Synuclein transfer between neurons and astrocytes indicates that astrocytes play a role in degradation rather than in spreading
Recent evidence suggests that disease progression in Parkinson’s disease (PD) could occur by the spreading of α-synuclein (α-syn) aggregates between neurons. Here we studied the role of astrocytes in the intercellular transfer and fate of α-syn fibrils, using in vitro and ex vivo models. α-Syn fibri...
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Veröffentlicht in: | Acta neuropathologica 2017-11, Vol.134 (5), p.789-808 |
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creator | Loria, Frida Vargas, Jessica Y. Bousset, Luc Syan, Sylvie Salles, Audrey Melki, Ronald Zurzolo, Chiara |
description | Recent evidence suggests that disease progression in Parkinson’s disease (PD) could occur by the spreading of α-synuclein (α-syn) aggregates between neurons. Here we studied the role of astrocytes in the intercellular transfer and fate of α-syn fibrils, using in vitro and ex vivo models. α-Syn fibrils can be transferred to neighboring cells; however, the transfer efficiency changes depending on the cell types. We found that α-syn is efficiently transferred from astrocytes to astrocytes and from neurons to astrocytes, but less efficiently from astrocytes to neurons. Interestingly, α-syn puncta are mainly found inside the lysosomal compartments of the recipient cells. However, differently from neurons, astrocytes are able to efficiently degrade fibrillar α-syn, suggesting an active role for these cells in clearing α-syn deposits. Astrocytes co-cultured with organotypic brain slices are able to take up α-syn fibrils from the slices. Altogether our data support a role for astrocytes in trapping and clearing α-syn pathological deposits in PD. |
doi_str_mv | 10.1007/s00401-017-1746-2 |
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Here we studied the role of astrocytes in the intercellular transfer and fate of α-syn fibrils, using in vitro and ex vivo models. α-Syn fibrils can be transferred to neighboring cells; however, the transfer efficiency changes depending on the cell types. We found that α-syn is efficiently transferred from astrocytes to astrocytes and from neurons to astrocytes, but less efficiently from astrocytes to neurons. Interestingly, α-syn puncta are mainly found inside the lysosomal compartments of the recipient cells. However, differently from neurons, astrocytes are able to efficiently degrade fibrillar α-syn, suggesting an active role for these cells in clearing α-syn deposits. Astrocytes co-cultured with organotypic brain slices are able to take up α-syn fibrils from the slices. Altogether our data support a role for astrocytes in trapping and clearing α-syn pathological deposits in PD.</description><identifier>ISSN: 0001-6322</identifier><identifier>EISSN: 1432-0533</identifier><identifier>DOI: 10.1007/s00401-017-1746-2</identifier><identifier>PMID: 28725967</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>alpha-Synuclein - metabolism ; Animals ; Astrocytes ; Astrocytes - metabolism ; Astrocytes - pathology ; Brain slice preparation ; Cells, Cultured ; Cellular Biology ; Coculture Techniques ; Disease Progression ; Fibrils ; Hippocampus - metabolism ; Hippocampus - pathology ; Life Sciences ; Medicine ; Medicine & Public Health ; Mice ; Movement disorders ; Neurobiology ; Neurodegenerative diseases ; Neurons ; Neurons - metabolism ; Neurons - pathology ; Neurons and Cognition ; Neurosciences ; Original Paper ; Parkinson Disease - metabolism ; Parkinson Disease - pathology ; Parkinson's disease ; Pathology ; Spreading ; Synuclein</subject><ispartof>Acta neuropathologica, 2017-11, Vol.134 (5), p.789-808</ispartof><rights>Springer-Verlag GmbH Germany 2017</rights><rights>Acta Neuropathologica is a copyright of Springer, 2017.</rights><rights>Attribution - NonCommercial</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c453t-2045d3a7f5d7a2894132236943f76a9562a4467a0e8891c950815f2580cae5743</citedby><cites>FETCH-LOGICAL-c453t-2045d3a7f5d7a2894132236943f76a9562a4467a0e8891c950815f2580cae5743</cites><orcidid>0000-0002-0433-4337 ; 0000-0001-6048-6602</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00401-017-1746-2$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00401-017-1746-2$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>230,314,776,780,881,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28725967$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://pasteur.hal.science/pasteur-01568774$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Loria, Frida</creatorcontrib><creatorcontrib>Vargas, Jessica Y.</creatorcontrib><creatorcontrib>Bousset, Luc</creatorcontrib><creatorcontrib>Syan, Sylvie</creatorcontrib><creatorcontrib>Salles, Audrey</creatorcontrib><creatorcontrib>Melki, Ronald</creatorcontrib><creatorcontrib>Zurzolo, Chiara</creatorcontrib><title>α-Synuclein transfer between neurons and astrocytes indicates that astrocytes play a role in degradation rather than in spreading</title><title>Acta neuropathologica</title><addtitle>Acta Neuropathol</addtitle><addtitle>Acta Neuropathol</addtitle><description>Recent evidence suggests that disease progression in Parkinson’s disease (PD) could occur by the spreading of α-synuclein (α-syn) aggregates between neurons. 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Here we studied the role of astrocytes in the intercellular transfer and fate of α-syn fibrils, using in vitro and ex vivo models. α-Syn fibrils can be transferred to neighboring cells; however, the transfer efficiency changes depending on the cell types. We found that α-syn is efficiently transferred from astrocytes to astrocytes and from neurons to astrocytes, but less efficiently from astrocytes to neurons. Interestingly, α-syn puncta are mainly found inside the lysosomal compartments of the recipient cells. However, differently from neurons, astrocytes are able to efficiently degrade fibrillar α-syn, suggesting an active role for these cells in clearing α-syn deposits. Astrocytes co-cultured with organotypic brain slices are able to take up α-syn fibrils from the slices. 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subjects | alpha-Synuclein - metabolism Animals Astrocytes Astrocytes - metabolism Astrocytes - pathology Brain slice preparation Cells, Cultured Cellular Biology Coculture Techniques Disease Progression Fibrils Hippocampus - metabolism Hippocampus - pathology Life Sciences Medicine Medicine & Public Health Mice Movement disorders Neurobiology Neurodegenerative diseases Neurons Neurons - metabolism Neurons - pathology Neurons and Cognition Neurosciences Original Paper Parkinson Disease - metabolism Parkinson Disease - pathology Parkinson's disease Pathology Spreading Synuclein |
title | α-Synuclein transfer between neurons and astrocytes indicates that astrocytes play a role in degradation rather than in spreading |
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