Full metadata record
DC Field | Value | Language |
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dc.contributor.author | Kim, J. | - |
dc.contributor.author | Kim, S.-J. | - |
dc.contributor.author | Jeong, H.-R. | - |
dc.contributor.author | Park, J.-H. | - |
dc.contributor.author | Moon, M. | - |
dc.contributor.author | Hoe, H.-S. | - |
dc.date.accessioned | 2022-11-30T18:10:10Z | - |
dc.date.available | 2022-11-30T18:10:10Z | - |
dc.date.created | 2022-11-17 | - |
dc.date.issued | 2022-10 | - |
dc.identifier.issn | 1664-3224 | - |
dc.identifier.uri | http://hdl.handle.net/20.500.11750/17208 | - |
dc.description.abstract | The FDA-approved EGFR/HER2 inhibitor varlitinib inhibits tumor growth and is used in cancer treatment. However, the neuroinflammatory response associated with EGFR/HER2 and its underlying mechanism have not been elucidated. This study evaluates the impact of varlitinib on LPS- and tau-mediated neuroinflammatory responses for the first time. In BV2 microglial cells, varlitinib reduced LPS-stimulated il-1β and/or inos mRNA levels and downstream AKT/FAK/NF-kB signaling. Importantly, varlitinib significantly diminished LPS-mediated microglial nlrp3 inflammasome activation in BV2 microglial cells. In primary astrocytes, varlitinib downregulated LPS-evoked astroglial il-1β mRNA levels, AKT signaling, and nlrp3 inflammasome activation. In LPS-treated wild-type mice, varlitinib significantly reduced LPS-stimulated glial activation and IL-1β/NLRP3 inflammasome formation. Moreover, varlitinib significantly reduced micro- and astroglial activation and tau hyperphosphorylation in 3-month-old tau-overexpressing PS19 mice by downregulating tau kinase DYRK1A levels. However, in 6-month-old tau-overexpressing PS19 mice, varlitinib only significantly diminished astroglial activation and tau phosphorylation at Thr212/Ser214. Taken together, our findings suggest that varlitinib has therapeutic potential for LPS- and tau-induced neuroinflammatory responses and the early stages of tau pathology. Copyright © 2022 Kim, Kim, Jeong, Park, Moon and Hoe. | - |
dc.language | English | - |
dc.publisher | Frontiers Media S.A. | - |
dc.title | Inhibiting EGFR/HER-2 ameliorates neuroinflammatory responses and the early stage of tau pathology through DYRK1A | - |
dc.type | Article | - |
dc.identifier.doi | 10.3389/fimmu.2022.903309 | - |
dc.identifier.scopusid | 2-s2.0-85141130742 | - |
dc.identifier.bibliographicCitation | Frontiers in Immunology, v.13 | - |
dc.description.isOpenAccess | FALSE | - |
dc.subject.keywordAuthor | Akt | - |
dc.subject.keywordAuthor | DYRK1A | - |
dc.subject.keywordAuthor | FAK | - |
dc.subject.keywordAuthor | LPS | - |
dc.subject.keywordAuthor | microglia | - |
dc.subject.keywordAuthor | NLRP3 | - |
dc.subject.keywordAuthor | tau | - |
dc.subject.keywordAuthor | varlitinib | - |
dc.subject.keywordPlus | GROWTH-FACTOR RECEPTOR | - |
dc.subject.keywordPlus | NF-KAPPA-B | - |
dc.subject.keywordPlus | EGF RECEPTOR | - |
dc.subject.keywordPlus | NLRP3 INFLAMMASOME | - |
dc.subject.keywordPlus | KINASE-ACTIVITY | - |
dc.subject.keywordPlus | TLR4 | - |
dc.subject.keywordPlus | ASTROCYTES | - |
dc.subject.keywordPlus | ACTIVATION | - |
dc.subject.keywordPlus | DISEASE | - |
dc.subject.keywordPlus | CELLS | - |
dc.citation.title | Frontiers in Immunology | - |
dc.citation.volume | 13 | - |
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