The cleavage effect of mesenchymal stem cell and its derived matrix metalloproteinase-2 on extracellular α-synuclein aggregates in parkinsonian models

Se Hee Oh, Ha Na Kim, Hyun Jung Park, Jin Young Shin, Dong Yeol Kim, philhyu Lee

Research output: Contribution to journalArticle

4 Citations (Scopus)

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 extracellularα-synuclein.Whenpreformedα-synuclein aggregates were incubated with MSC-conditioned medium, α-synuclein aggregates were disassembled, and insoluble and oligomeric forms ofα-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 ofα-synuclein oligomers and the induction of pathogenicα-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 derivedMMP-2exert neuroprotective properties through proteolysis of aggregated α-synuclein in PD-related microenvironments.

Original languageEnglish
Pages (from-to)949-961
Number of pages13
JournalStem Cells Translational Medicine
Volume6
Issue number3
DOIs
Publication statusPublished - 2017 Mar 1

Fingerprint

Synucleins
Matrix Metalloproteinase 2
Mesenchymal Stromal Cells
Parkinsonian Disorders
Conditioned Culture Medium
Proteolysis
Neuroprotective Agents
Cell Death

All Science Journal Classification (ASJC) codes

  • Developmental Biology
  • Cell Biology

Cite this

@article{b94f548da98a4cbcb8dda080fe4d7405,
title = "The cleavage effect of mesenchymal stem cell and its derived matrix metalloproteinase-2 on extracellular α-synuclein aggregates in parkinsonian models",
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 extracellularα-synuclein.Whenpreformedα-synuclein aggregates were incubated with MSC-conditioned medium, α-synuclein aggregates were disassembled, and insoluble and oligomeric forms ofα-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 ofα-synuclein oligomers and the induction of pathogenicα-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 derivedMMP-2exert neuroprotective properties through proteolysis of aggregated α-synuclein in PD-related microenvironments.",
author = "Oh, {Se Hee} and Kim, {Ha Na} and Park, {Hyun Jung} and Shin, {Jin Young} and Kim, {Dong Yeol} and philhyu Lee",
year = "2017",
month = "3",
day = "1",
doi = "10.5966/sctm.2016-0111",
language = "English",
volume = "6",
pages = "949--961",
journal = "Stem cells translational medicine",
issn = "2157-6564",
publisher = "AlphaMed Press",
number = "3",

}

The cleavage effect of mesenchymal stem cell and its derived matrix metalloproteinase-2 on extracellular α-synuclein aggregates in parkinsonian models. / Oh, Se Hee; Kim, Ha Na; Park, Hyun Jung; Shin, Jin Young; Kim, Dong Yeol; Lee, philhyu.

In: Stem Cells Translational Medicine, Vol. 6, No. 3, 01.03.2017, p. 949-961.

Research output: Contribution to journalArticle

TY - JOUR

T1 - The cleavage effect of mesenchymal stem cell and its derived matrix metalloproteinase-2 on extracellular α-synuclein aggregates in parkinsonian models

AU - Oh, Se Hee

AU - Kim, Ha Na

AU - Park, Hyun Jung

AU - Shin, Jin Young

AU - Kim, Dong Yeol

AU - Lee, philhyu

PY - 2017/3/1

Y1 - 2017/3/1

N2 - 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 extracellularα-synuclein.Whenpreformedα-synuclein aggregates were incubated with MSC-conditioned medium, α-synuclein aggregates were disassembled, and insoluble and oligomeric forms ofα-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 ofα-synuclein oligomers and the induction of pathogenicα-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 derivedMMP-2exert neuroprotective properties through proteolysis of aggregated α-synuclein in PD-related microenvironments.

AB - 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 extracellularα-synuclein.Whenpreformedα-synuclein aggregates were incubated with MSC-conditioned medium, α-synuclein aggregates were disassembled, and insoluble and oligomeric forms ofα-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 ofα-synuclein oligomers and the induction of pathogenicα-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 derivedMMP-2exert neuroprotective properties through proteolysis of aggregated α-synuclein in PD-related microenvironments.

UR - http://www.scopus.com/inward/record.url?scp=85017551363&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85017551363&partnerID=8YFLogxK

U2 - 10.5966/sctm.2016-0111

DO - 10.5966/sctm.2016-0111

M3 - Article

VL - 6

SP - 949

EP - 961

JO - Stem cells translational medicine

JF - Stem cells translational medicine

SN - 2157-6564

IS - 3

ER -