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Mesenchymal stem cells modulate misfolded α-synuclein in parkinsonian disorders: A multitarget disease-modifying strategy

Authors
 Jin Young Shin  ;  Phil Hyu Lee 
Citation
 STEM CELL RESEARCH, Vol.47 : 101908, 2020-08 
Journal Title
 STEM CELL RESEARCH 
ISSN
 1873-5061 
Issue Date
2020-08
Keywords
Disease-modifying therapy ; Mesenchymal stem cells ; Neurodegeneration ; Parkinsonian disorders ; α-Synuclein
Abstract
α-Synuclein (α-Syn) aggregates, the major toxic component of Lewy bodies, are proteinaceous fibrillar cytoplasmic inclusions observed in α-synucleinopathies, such as Parkinson's disease (PD), multiple system atrophy, and dementia with Lewy bodies. Overexpression of α-syn induce neuronal loss and α-syn aggregation in PD animals. Recent studies show that α-syn is released by exocytosis and can be transmitted between brain areas through cell-to-cell propagation. Moreover, aggregates of extracellular α-syn can induce neuroinflammation-mediated neurotoxic signaling through microglial activation and release of pro-inflammatory factors. Thus, modulation of α-syn might be a potential therapeutic strategy for modifying disease progression of α-synucleinopathies. Our previous studies have revealed that MSCs have potent neuroprotective effects in PD animal through modulation of neuroinflammation, inhibition of cell death, and promotion of neurogenesis. Here, we provide further evidence that MSCs have the potential to modulate α-syn-related microenvironments via enhancement of autophagy, proteolysis of α-syn aggregates, inhibition of cell-to-cell transmission of α-syn, stabilization of axonal transport, and phagocytic clearance of α-syn by microglial M2 polarization. With advantages in clinical applications, these data suggests that the use of MSCs as pharmacological modulators of α-syn propagation would be an effective therapeutic approach in PD.
Full Text
https://www.sciencedirect.com/science/article/pii/S1873506120302099
DOI
10.1016/j.scr.2020.101908
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)
Lee, Phil Hyu(이필휴) ORCID logo https://orcid.org/0000-0001-9931-8462
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/181470
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