title: Mesenchymal Stem Cells Inhibit Transmission of α-Synuclein by Modulating Clathrin-Mediated Endocytosis in a Parkinsonian Model.
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.
authors.affiliation: Department of Neurology, College of Medicine, Yonsei University, Seoul 120-752, Korea.
authors.forename: Se Hee
authors.initials: SH
authors.lastname: Oh
authors.affiliation: Department of Neurology, College of Medicine, Yonsei University, Seoul 120-752, Korea.
authors.forename: Ha Na
authors.initials: HN
authors.lastname: Kim
authors.affiliation: Department of Neurology, College of Medicine, Yonsei University, Seoul 120-752, Korea; Severance Biomedical Science Institute, Yonsei University, Seoul 120-752, Korea.
authors.forename: Hyun Jung
authors.initials: HJ
authors.lastname: Park
authors.affiliation: Department of Neurology, College of Medicine, Yonsei University, Seoul 120-752, Korea; Severance Biomedical Science Institute, Yonsei University, Seoul 120-752, Korea.
authors.forename: Jin Young
authors.initials: JY
authors.lastname: Shin
authors.affiliation: Department of Medicine, Neuroscience Research Institute,Seoul National University College of Medicine, Seoul 110-799, Korea.
authors.forename: Eun-Jin
authors.initials: EJ
authors.lastname: Bae
authors.affiliation: Department of Neurology, Bundang Jesaeng General Hospital, Seongnam 463-774, Korea.
authors.forename: Mun Kyung
authors.initials: MK
authors.lastname: Sunwoo
authors.affiliation: Department of Medicine, Neuroscience Research Institute,Seoul National University College of Medicine, Seoul 110-799, Korea.
authors.forename: Seung-Jae
authors.initials: SJ
authors.lastname: Lee
authors.affiliation: 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.
authors.forename: Phil Hyu
authors.initials: PH
authors.lastname: Lee
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D002966:Clathrin / Q000378:metabolism*; D059290:Dopaminergic Neurons / Q000378:metabolism; D004705:Endocytosis; D037483:Galectin 1 / Q000378:metabolism; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D010300:Parkinson Disease / Q000378:metabolism*; D011485:Protein Binding; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D051844:alpha-Synuclein / Q000378:metabolism*
chemical_list: D002966:Clathrin; D037483:Galectin 1; D016194:Receptors, N-Methyl-D-Aspartate; D051844:alpha-Synuclein