Full metadata record
DC Field | Value | Language |
---|---|---|
dc.contributor.author | 김희선 | * |
dc.date.accessioned | 2016-08-28T12:08:21Z | - |
dc.date.available | 2016-08-28T12:08:21Z | - |
dc.date.issued | 2010 | * |
dc.identifier.issn | 0022-1767 | * |
dc.identifier.other | OAK-6648 | * |
dc.identifier.uri | https://dspace.ewha.ac.kr/handle/2015.oak/220853 | - |
dc.description.abstract | The mutation or overexpression of α-synuclein protein plays a pivotal role in the pathogenesis of Parkinson's disease. In our preliminary experiments, we found that α-synuclein induced the expression of matrix metalloproteinases (MMPs) (MMP-1, -3, -8, and -9) in rat primary cultured microglia. Thus, the current study was undertaken to determine the roles of MMPs in α-synuclein - induced microglial activation. The inhibition of MMP-3, -8, or -9 significantly reduced NO and reactive oxygen species levels and suppressed the expression of TNF-α and IL-1β. Notably, MMP-8 inhibitor suppressed TNF-α production more efficaciously than MMP-3 or MMP-9 inhibitors. Inhibition of MMP-3 or -9 also suppressed the activities of MAPK, NF-κB, and AP-1. Previously, protease-activated receptor-1 (PAR-1) has been associated with the actions of MMPs, and thus, we further investigated the role of PAR-1 in α-synuclein-induced inflammatory reactions. A PAR-1-specific inhibitor and a PAR-1 antagonist significantly suppressed cytokine levels, and NO and reactive oxygen species production in α-synuclein-treated microglia. Subsequent PAR-1 cleavage assay revealed that MMP-3, -8, and -9, but not α-synuclein, cleaved the synthetic peptide containing conventional PAR-1 cleavage sites. These results suggest that MMPs secreted by α-synuclein-stimulated microglia activate PAR-1 and amplify microglial inflammatory signals in an autocrine or paracrine manner. Furthermore, our findings suggest that modulation of the activities of MMPs and/or PAR-1 may provide a new therapeutic strategy for Parkinson's disease. Copyright © 2010 by The American Association of Immunologists, Inc. | * |
dc.language | English | * |
dc.title | α-synuclein activates microglia by inducing the expressions of matrix metalloproteinases and the subsequent activation of protease-activated receptor-1 | * |
dc.type | Article | * |
dc.relation.issue | 1 | * |
dc.relation.volume | 185 | * |
dc.relation.index | SCI | * |
dc.relation.index | SCIE | * |
dc.relation.index | SCOPUS | * |
dc.relation.startpage | 615 | * |
dc.relation.lastpage | 623 | * |
dc.relation.journaltitle | Journal of Immunology | * |
dc.identifier.doi | 10.4049/jimmunol.0903480 | * |
dc.identifier.wosid | WOS:000278933800067 | * |
dc.identifier.scopusid | 2-s2.0-77956194977 | * |
dc.author.google | Lee E.-J. | * |
dc.author.google | Woo M.-S. | * |
dc.author.google | Moon P.-G. | * |
dc.author.google | Baek M.-C. | * |
dc.author.google | Choi I.-Y. | * |
dc.author.google | Kim W.-K. | * |
dc.author.google | Junn E. | * |
dc.author.google | Kim H.-S. | * |
dc.contributor.scopusid | 김희선(57191372551) | * |
dc.date.modifydate | 20240118140922 | * |