title: Neuroprotective effects of mesenchymal stem cells through autophagy modulation in a parkinsonian model.
abstract: Autophagy is a major degradation pathway for abnormal aggregated proteins and organelles that cause various neurodegenerative diseases. Current evidence suggests a central role for autophagy in pathogenesis of Parkinson's disease, and that dysfunction in the autophagic system may lead to α-synuclein accumulation. In the present study, we investigated whether mesenchymal stem cells (MSCs) would enhance autophagy and thus exert a neuroprotective effect through the modulation of α-synuclein in parkinsonian models. In MPP(+)-treated neuronal cells, coculture with MSCs increased cellular viability, attenuated expression of α-synuclein, and enhanced the number of LC3-II-positive autophagosomes compared with cells treated with MPP(+) only. In an MPTP-treated animal model of Parkinson's disease, MSC administration significantly increased final maturation of late autophagic vacuoles, fusion with lysosomes. Moreover, MSC administration significantly reduced the level of α-synuclein in dopaminergic neurons, which was elevated in MPTP-treated mice. These results suggest that MSC treatment significantly enhances autophagolysosome formation and may modulate α-synuclein expression in parkinsonian models, which may lead to increased neuronal survival in the presence of neurotoxins.
authors.affiliation: Department of Neurology and Brain Research Institute, Yonsei University College, Seoul, South Korea; Severance Biomedical Science Institute, Yonsei University, Seoul, South Korea.
authors.forename: Hyun Jung
authors.initials: HJ
authors.lastname: Park
authors.affiliation: Department of Neurology and Brain Research Institute, Yonsei University College, Seoul, South Korea; Severance Biomedical Science Institute, Yonsei University, Seoul, South Korea.
authors.forename: Jin Young
authors.initials: JY
authors.lastname: Shin
authors.affiliation: Department of Neurology and Brain Research Institute, Yonsei University College, Seoul, South Korea; Severance Biomedical Science Institute, Yonsei University, Seoul, South Korea.
authors.forename: Ha Na
authors.initials: HN
authors.lastname: Kim
authors.affiliation: Department of Neurology and Brain Research Institute, Yonsei University College, Seoul, South Korea; Severance Biomedical Science Institute, Yonsei University, Seoul, South Korea.
authors.forename: Se Hee
authors.initials: SH
authors.lastname: Oh
authors.affiliation: Department of Neurology and Brain Research Institute, Yonsei University College, Seoul, South Korea; Severance Biomedical Science Institute, Yonsei University, Seoul, South Korea. Electronic address: phisland@chol.net.
authors.forename: Phil Hyu
authors.initials: PH
authors.lastname: Lee
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000009:adverse effects; D015655:1-Methyl-4-phenylpyridinium / Q000009:adverse effects; D000818:Animals; D001343:Autophagy / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004195:Disease Models, Animal; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D008810:Mice, Inbred C57BL; D009498:Neurotoxins / Q000009:adverse effects; D010300:Parkinson Disease / Q000209:etiology / Q000378:metabolism / Q000473:pathology* / Q000517:prevention & control*; D066329:Protein Aggregates; D066263:Protein Aggregation, Pathological; D051844:alpha-Synuclein / Q000378:metabolism
chemical_list: D009498:Neurotoxins; D066329:Protein Aggregates; D051844:alpha-Synuclein; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D015655:1-Methyl-4-phenylpyridinium
keywords: Autophagolysosome formation; Autophagy; Mesenchymal stem cells; Parkinson's disease; α-Synuclein