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

Se Hee Oh, Ha Na Kim, Hyun Jung Park, Jin Young Shin, Eun Jin Bae, Mun Kyung Sunwoo, Seung Jae Lee, philhyu Lee

Research output: Contribution to journalArticle

21 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)835-849
Number of pages15
JournalCell Reports
Volume14
Issue number4
DOIs
Publication statusPublished - 2016 Feb 2

Fingerprint

Synucleins
Clathrin
Endocytosis
Stem cells
Mesenchymal Stromal Cells
Galectin 1
Prions
Dopaminergic Neurons
N-Methyl-D-Aspartate Receptors
Neurons
Brain
Modulation

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Oh, Se Hee ; Kim, Ha Na ; Park, Hyun Jung ; Shin, Jin Young ; Bae, Eun Jin ; Sunwoo, Mun Kyung ; Lee, Seung Jae ; Lee, philhyu. / Mesenchymal Stem Cells Inhibit Transmission of α-Synuclein by Modulating Clathrin-Mediated Endocytosis in a Parkinsonian Model. In: Cell Reports. 2016 ; Vol. 14, No. 4. pp. 835-849.
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Mesenchymal Stem Cells Inhibit Transmission of α-Synuclein by Modulating Clathrin-Mediated Endocytosis in a Parkinsonian Model. / Oh, Se Hee; Kim, Ha Na; Park, Hyun Jung; Shin, Jin Young; Bae, Eun Jin; Sunwoo, Mun Kyung; Lee, Seung Jae; Lee, philhyu.

In: Cell Reports, Vol. 14, No. 4, 02.02.2016, p. 835-849.

Research output: Contribution to journalArticle

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AU - Oh, Se Hee

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AU - Shin, Jin Young

AU - Bae, Eun Jin

AU - Sunwoo, Mun Kyung

AU - Lee, Seung Jae

AU - Lee, philhyu

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