Inhibiting EGFR/HER-2 ameliorates neuroinflammatory responses and the early stage of tau pathology through DYRK1A
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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.
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Vallitinib has therapeutic potential in the context of lipopolysaccharide- and hyper-repeat-protein-induced neuroinflammatory responses and the early stages of tau protein pathology.
“Vallitinib, an epidermal growth factor receptor (EGFR)/HER2 inhibitor, has therapeutic potential in the context of lipopolysaccharide- and hyper-repeat-protein-induced neuroinflammatory responses and the early stages of tau protein pathology.”
From Role of Tau Protein in Neurodegenerative Diseases and Development of Its Targeted Drugs: A Literature Review (2024) · cites this paper as [203]
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- Authors
- Kim, J., Kim, S.-J., Jeong, H.-R., Park, J.-H., Moon, M., & Hoe, H.-S.
- Affiliations
- Korea Brain Research Institute (KR)
- Daegu Gyeongbuk Institute of Science and Technology (KR)
- Konyang University (KR)
- Corresponding author
- Moon, Minho
- Hoe, Hyang-Sook
- Venue
- Frontiers in Immunology
- Publisher
- Frontiers Media SA
- Published
- 2022-10-20
- Volume
- 13
- Pages
- 903309-903309
- ISSN
- 1664-3224 (ISSN-L)
- PMC
- PMC9632417
- OpenAlex
- W4306879915
- Cited by
- 23
- References
- 69
- Citations by year
- 2026: 9 · 2025: 3 · 2024: 4 · 2023: 6 · 2012: 1
- FWCI
- 1.14
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Immunology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
- Keywords
- neuroinflammation, tau pathology, DYRK1A, NLRP3 inflammasome, microglial activation, astroglial activation, IL-1β, tau hyperphosphorylation, Akt signaling, NF-κB signaling, lipopolysaccharide, Alzheimer's disease
- MeSH terms
- NLR Family, Pyrin Domain-Containing 3 Protein, Animals, Inflammation, Lipopolysaccharides, RNA, Messenger, Protein Kinase Inhibitors, Proto-Oncogene Proteins c-akt, Mice, Inflammasomes, ErbB Receptors
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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