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

Se Hee Oh, Seok Cheol Lee, Dong Yeol Kim, Ha Na Kim, Jin Young Shin, Byoung Seok Ye, Phil Hyu Lee

Research output: Contribution to journalArticle

8 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1934-1947
Number of pages14
JournalStem Cells
Volume35
Issue number8
DOIs
Publication statusPublished - 2017 Aug

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Developmental Biology
  • Cell Biology

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