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Cell Rep. 2016 Feb 2;14(4):835-849. doi: 10.1016/j.celrep.2015.12.075. Epub 2016 Jan 14.

Mesenchymal Stem Cells Inhibit Transmission of α-Synuclein by Modulating Clathrin-Mediated Endocytosis in a Parkinsonian Model.

Author information

1
Department of Neurology, College of Medicine, Yonsei University, Seoul 120-752, Korea.
2
Department of Neurology, College of Medicine, Yonsei University, Seoul 120-752, Korea; Severance Biomedical Science Institute, Yonsei University, Seoul 120-752, Korea.
3
Department of Medicine, Neuroscience Research Institute,Seoul National University College of Medicine, Seoul 110-799, Korea.
4
Department of Neurology, Bundang Jesaeng General Hospital, Seongnam 463-774, Korea.
5
Department of Neurology, College of Medicine, Yonsei University, Seoul 120-752, Korea; Severance Biomedical Science Institute, Yonsei University, Seoul 120-752, Korea. Electronic address: phisland@chol.net.

Abstract

Ample evidence suggests that α-synuclein is released from cells and propagated from one area of the brain to others via cell-to-cell transmission. In terms of their prion-like behavior, α-synuclein propagation plays key roles in the pathogenesis and progression of α-synucleinopathies. Using α-synuclein-enriched models, we show that mesenchymal stem cells (MSCs) inhibited α-synuclein transmission by blocking the clathrin-mediated endocytosis of extracellular α-synuclein via modulation of the interaction with N-methyl-D-aspartate receptors, which led to a prosurvival effect on cortical and dopaminergic neurons with functional improvement of motor deficits in α-synuclein-enriched models. Furthermore, we identify that galectin-1, a soluble factor derived from MSCs, played an important role in the transmission control of aggregated α-synuclein in these models. The present data indicated that MSCs exert neuroprotective properties through inhibition of extracellular α-synuclein transmission, suggesting that the property of MSCs may act as a disease-modifying therapy in subjects with α-synucleinopathies.

PMID:
26776513
DOI:
10.1016/j.celrep.2015.12.075
[Indexed for MEDLINE]
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