Open AccessMesenchymal Stem Cells Stabilize Axonal Transports for Autophagic Clearance of α‐Synuclein in Parkinsonian Models
Author(s) -
Oh Se Hee,
Lee Seok Cheol,
Kim Dong Yeol,
Kim Ha Na,
Shin Jin Young,
Ye Byoung Seok,
Lee Phil Hyu
Publication year - 2017
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.2650
Subject(s) - biology , microbiology and biotechnology , synucleinopathies , mesenchymal stem cell , axoplasmic transport , phosphorylation , neuroprotection , alpha synuclein , autophagy , microtubule , dopaminergic , neuroscience , parkinson's disease , dopamine , pathology , biochemistry , apoptosis , disease , medicine
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. S tem C ells 2017;35:1934–1947