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The Cleavage Effect of Mesenchymal Stem Cell and Its Derived Matrix Metalloproteinase-2 on Extracellular α-Synuclein Aggregates in Parkinsonian Models

Authors
 Se Hee Oh  ;  Ha Na Kim  ;  Hyun Jung Park  ;  Jin Young Shin  ;  Dong Yeol Kim  ;  Phil Hyu Lee 
Citation
 STEM CELLS TRANSLATIONAL MEDICINE, Vol.6(3) : 949-961, 2017 
Journal Title
STEM CELLS TRANSLATIONAL MEDICINE
ISSN
 2157-6564 
Issue Date
2017
Keywords
Matrix metalloproteinase-2 ; Mesenchymal stem cell ; Parkinson’s disease ; Proteolysis ; α-Synuclein
Abstract
Ample evidence has suggested that extracellular α-synuclein aggregates would play key roles in the pathogenesis and progression of Parkinsonian disorders (PDs). In the present study, we investigated whether mesenchymal stem cells (MSCs) and their derived soluble factors could exert neuroprotective effects via proteolysis of extracellular α-synuclein. When preformed α-synuclein aggregates were incubated with MSC-conditioned medium, α-synuclein aggregates were disassembled, and insoluble and oligomeric forms of α-synuclein were markedly decreased, thus leading to a significant increase in neuronal viability. In an animal study, MSC or MSC-conditioned medium treatment decreased the expression of α-synuclein oligomers and the induction of pathogenic α-synuclein with an attenuation of apoptotic cell death signaling. Furthermore, we identified that matrix metalloproteinase-2 (MMP-2), a soluble factor derived from MSCs, played an important role in the degradation of extracellular α-synuclein. Our data demonstrated that MSCs and their derived MMP-2 exert neuroprotective properties through proteolysis of aggregated α-synuclein in PD-related microenvironments. Stem Cells Translational Medicine 2017;6:949-961.
Files in This Item:
T201700631.pdf Download
DOI
10.5966/sctm.2016-0111
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Neurology (신경과학교실) > 1. Journal Papers
Yonsei Authors
Lee, Phil Hyu(이필휴) ORCID logo https://orcid.org/0000-0001-9931-8462
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/154670
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