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
Hauptverfasser: Loria, Frida, Vargas, Jessica Y., Bousset, Luc, Syan, Sylvie, Salles, Audrey, Melki, Ronald, Zurzolo, Chiara
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container_issue 5
container_start_page 789
container_title Acta neuropathologica
container_volume 134
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.
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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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