N,N-disubstituted azines attenuate LPS-mediated neuroinflammation in microglia and neuronal apoptosis via inhibiting MAPK signaling pathways
DC Field | Value | Language |
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dc.contributor.author | Subedi, Lalita | - |
dc.contributor.author | Kwon, Oh Wook | - |
dc.contributor.author | Pak, Chaeho | - |
dc.contributor.author | Lee, Goeun | - |
dc.contributor.author | Lee, Kangwoo | - |
dc.contributor.author | Kim, Hakwon | - |
dc.contributor.author | Kim, Sun Yeou | - |
dc.date.available | 2020-02-27T16:41:13Z | - |
dc.date.created | 2020-02-06 | - |
dc.date.issued | 2017-12-28 | - |
dc.identifier.issn | 1471-2202 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/5363 | - |
dc.description.abstract | Background: Activated microglia interact with astrocytes and neuronal cells to induce neuroinflammation, which can contribute to the pathogenesis and progression of Alzheimer's and Parkinson's disease. To identify the most effective anti-neuroinflammatory agent, we designed and synthesized a family of 13 new azine derivatives and investigated their anti-neuroinflammatory activities in LPS-activated BV-2 microglial cells. Results: Out of 13 derivatives, compound 3 [4,4'-(1E, 1'E, 3E, 3'E)-3,3'-(hydrazine-1,2-diylidene) bis-(prop-1-ene-1-yl-3-ylidene) bis-(2-methoxyphenol)] exhibited excellent anti-neuroinflammatory activities (IC50 = 12.47 mu M), which protected neurons from microglia-mediated neurotoxicity. Specifically, the anti-neuroinflammatory effects of compound 3 inhibited MAPK signaling pathways through the inhibition of p38 and JNK mediated signaling and the production of pro-inflammatory cytokines, and inflammatory mediators. Additionally, compound 3 strongly exhibited neuroprotective effect by inhibiting LPS-mediated necrosis and apoptosis. Preliminary SAR analysis suggests that the presence of methoxyphenol and the substitution pattern within hydrazine may influence the anti-neuroinflammatory activity. FACS analysis also strongly supports the neuroprotective effect of compound 3. Conclusions: Based on our results, the compound 3 exhibited excellent anti-neuroinflammatory activity against LPS-activated microglia, which resulted in the inhibition of neuronal apoptosis and neuronal degeneration. | - |
dc.language | 영어 | - |
dc.language.iso | en | - |
dc.publisher | BMC | - |
dc.relation.isPartOf | BMC NEUROSCIENCE | - |
dc.subject | NITRIC-OXIDE | - |
dc.subject | CELL-DEATH | - |
dc.subject | INFLAMMATION | - |
dc.subject | BRAIN | - |
dc.subject | CYCLOOXYGENASE-2 | - |
dc.subject | ACTIVATION | - |
dc.subject | MECHANISMS | - |
dc.subject | HYDRAZINE | - |
dc.subject | RESPONSES | - |
dc.subject | MOLECULE | - |
dc.title | N,N-disubstituted azines attenuate LPS-mediated neuroinflammation in microglia and neuronal apoptosis via inhibiting MAPK signaling pathways | - |
dc.type | Article | - |
dc.type.rims | ART | - |
dc.description.journalClass | 1 | - |
dc.identifier.wosid | 000418876500002 | - |
dc.identifier.doi | 10.1186/s12868-017-0399-3 | - |
dc.identifier.bibliographicCitation | BMC NEUROSCIENCE, v.18 | - |
dc.identifier.scopusid | 2-s2.0-85039853963 | - |
dc.citation.title | BMC NEUROSCIENCE | - |
dc.citation.volume | 18 | - |
dc.contributor.affiliatedAuthor | Pak, Chaeho | - |
dc.contributor.affiliatedAuthor | Kim, Sun Yeou | - |
dc.type.docType | Article | - |
dc.subject.keywordAuthor | Azine | - |
dc.subject.keywordAuthor | Lipopolysaccharide | - |
dc.subject.keywordAuthor | Neuroinflammation | - |
dc.subject.keywordAuthor | MAPK | - |
dc.subject.keywordAuthor | Apoptosis | - |
dc.subject.keywordPlus | NITRIC-OXIDE | - |
dc.subject.keywordPlus | CELL-DEATH | - |
dc.subject.keywordPlus | INFLAMMATION | - |
dc.subject.keywordPlus | BRAIN | - |
dc.subject.keywordPlus | CYCLOOXYGENASE-2 | - |
dc.subject.keywordPlus | ACTIVATION | - |
dc.subject.keywordPlus | MECHANISMS | - |
dc.subject.keywordPlus | HYDRAZINE | - |
dc.subject.keywordPlus | RESPONSES | - |
dc.subject.keywordPlus | MOLECULE | - |
dc.relation.journalResearchArea | Neurosciences & Neurology | - |
dc.relation.journalWebOfScienceCategory | Neurosciences | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
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