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Acta Neuropathol. 2017 Nov;134(5):789-808. doi: 10.1007/s00401-017-1746-2. Epub 2017 Jul 19.

α-Synuclein transfer between neurons and astrocytes indicates that astrocytes play a role in degradation rather than in spreading.

Author information

1
Unité de Trafic Membranaire et Pathogénèse, Institut Pasteur, Paris, France.
2
Paris-Saclay Institute of Neuroscience, CNRS, Gif-sur-Yvette, France.
3
Imagopole-Citech, Institut Pasteur, Paris, France.
4
Unité de Trafic Membranaire et Pathogénèse, Institut Pasteur, Paris, France. chiara.zurzolo@pasteur.fr.

Abstract

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.

KEYWORDS:

Intercellular spreading; Organotypic cultures; Parkinson’s disease; Primary cultures; α-Synuclein

PMID:
28725967
DOI:
10.1007/s00401-017-1746-2
[Indexed for MEDLINE]
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