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Mesenchymal Stem Cells Stabilize Axonal Transports for Autophagic Clearance of α-Synuclein in Parkinsonian Models

Authors
 Se Hee Oh  ;  Seok Cheol Lee  ;  Dong Yeol Kim  ;  Ha Na Kim  ;  Jin Young Shin  ;  Byoung Seok Ye  ;  Phil Hyu Lee 
Citation
 STEM CELLS, Vol.35(8) : 1934-1947, 2017 
Journal Title
STEM CELLS
ISSN
 1066-5099 
Issue Date
2017
MeSH
Animals ; Autophagy* ; Axonal Transport* ; Calcium/metabolism ; Calmodulin/metabolism ; Cell Line ; Dependovirus/metabolism ; Humans ; Male ; Mesenchymal Stromal Cells/metabolism* ; Mesenchymal Stromal Cells/ultrastructure ; Mice, Inbred C57BL ; Microtubules/metabolism ; Models, Biological* ; Mutation/genetics ; Parkinson Disease/metabolism* ; Parkinson Disease/pathology* ; Transfection ; alpha-Synuclein/metabolism*
Keywords
Autophagy ; Axonal transport ; Eukaryotic elongation factor 1A-2 ; Mesenchymal stem cell ; Microtubule ; Parkinson's disease ; α-Synuclein
Abstract
Genome-wide association studies have identified two loci, SNCA and the microtubule (MT)-associated protein tau, as common risk factors for Parkinson's disease (PD). Specifically, α-synuclein directly destabilizes MT via tau phosphorylation and induces axonal transport deficits that are the primary events leading to an abnormal accumulation of α-synuclein that causes nigral dopaminergic cell loss. In this study, we demonstrated that mesenchymal stem cells (MSCs) could modulate cytoskeletal networks and trafficking to exert neuroprotective properties in wild-type or A53T α-synuclein overexpressing cells and mice. Moreover, we found that eukaryotic elongation factor 1A-2, a soluble factor derived from MSCs, stabilized MT assembly by decreasing calcium/calmodulin-dependent tau phosphorylation and induced autophagolysosome fusion, which was accompanied by an increase in the axonal motor proteins and increased neuronal survival. Our data suggest that MSCs have beneficial effects on axonal transports via MT stability by controlling α-synuclein-induced tau phosphorylation, indicating that MSCs may exert a protective role in the early stages of axonal transport defects in α-synucleinopathies. Stem Cells 2017;35:1934-1947.
Full Text
https://stemcellsjournals.onlinelibrary.wiley.com/doi/abs/10.1002/stem.2650
DOI
10.1002/stem.2650
Appears in Collections:
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Neurology (신경과학교실) > 1. Journal Papers
Yonsei Authors
Shin, Jin Young(신진영)
Ye, Byoung Seok(예병석) ORCID logo https://orcid.org/0000-0003-0187-8440
Lee, Phil Hyu(이필휴) ORCID logo https://orcid.org/0000-0001-9931-8462
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/160400
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