Home > Documents in Process > Enhancing Tyro3 signaling ameliorates IL-1β production through STAT1 in Alzheimer's disease models. > print

001     282601
005     20251211160816.0
024 7 _ |a 10.1093/jleuko/qiaf157
|2 doi
024 7 _ |a pmid:41206011
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024 7 _ |a 0741-5400
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024 7 _ |a 1938-3673
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037 _ _ |a DZNE-2025-01359
041 _ _ |a English
082 _ _ |a 570
100 1 _ |a Ravichandran, Kishore Aravind
|0 P:(DE-2719)9002244
|b 0
|e First author
|u dzne
245 _ _ |a Enhancing Tyro3 signaling ameliorates IL-1β production through STAT1 in Alzheimer's disease models.
260 _ _ |a Tokyo
|c 2025
|b Oxford University Press
336 7 _ |a article
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336 7 _ |a ARTICLE
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336 7 _ |a Journal Article
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520 _ _ |a Neuroinflammation plays a vital role in determining the trajectory of Alzheimer's disease (AD) progression. In the AD brain, microglial exposure to pathological amyloid β (Aβ42) and tau peptide aggregates results in an NLRP3 inflammasome-activated proinflammatory response that ranges from mild to severe. Recently we have shown that dementia subjects with higher levels of soluble TAM receptors Tyro3 and AXL in the cerebrospinal fluid indicated cognitive protection. The molecular mechanism for this protective effect of TAM receptors is unknown. Here, we identified a beneficial role of TAM receptors using Tyro3-overexpressing (Tyro3OE) and Axl-overexpressing THP-1 cells. In the Tyro3OE cells, the levels of the proinflammatory cytokine IL-1β were markedly decreased in the AD microenvironment (tau + Aβ42) and the classical NLRP3 inflammasome model (lipopolysaccharide [LPS] + nigericin) in comparison with the control cells. This was mediated by increased STAT1 phosphorylation and reduced IL-1β transcription enhancer C-EBP-β in Tyro3OE cells. The use of the JAK1/2 inhibitor ruxolitinib reduced the phosphorylation of STAT1, leading to a partial restoration of IL-1β in the Tyro3OE cells. Last, we found a significantly reduced IL-1β in the brains of AD mice that has activated TAM signaling through Gas6-α-Aβ lentiviral injection. In summary, TAM receptor Tyro3 overexpression decreased AD-associated IL-1β release from macrophages thereby uncovering a potential beneficial role for TAM receptors during neuroinflammation in AD.
536 _ _ |a 353 - Clinical and Health Care Research (POF4-353)
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|c POF4-353
|f POF IV
|x 0
536 _ _ |a 352 - Disease Mechanisms (POF4-352)
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650 _ 7 |a AD
|2 Other
650 _ 7 |a Alzheimer’s disease
|2 Other
650 _ 7 |a IL-1β
|2 Other
650 _ 7 |a NLRP3
|2 Other
650 _ 7 |a TAM receptors
|2 Other
650 _ 7 |a Interleukin-1beta
|2 NLM Chemicals
650 _ 7 |a STAT1 Transcription Factor
|2 NLM Chemicals
650 _ 7 |a Receptor Protein-Tyrosine Kinases
|0 EC 2.7.10.1
|2 NLM Chemicals
650 _ 7 |a Amyloid beta-Peptides
|2 NLM Chemicals
650 _ 7 |a Inflammasomes
|2 NLM Chemicals
650 _ 7 |a Proto-Oncogene Proteins
|2 NLM Chemicals
650 _ 7 |a Axl Receptor Tyrosine Kinase
|2 NLM Chemicals
650 _ 7 |a Tyro3 protein, mouse
|0 EC 2.7.10.1
|2 NLM Chemicals
650 _ 7 |a TYRO3 protein, human
|0 EC 2.7.10.1
|2 NLM Chemicals
650 _ 7 |a Nitriles
|2 NLM Chemicals
650 _ 2 |a Alzheimer Disease: metabolism
|2 MeSH
650 _ 2 |a Alzheimer Disease: pathology
|2 MeSH
650 _ 2 |a Alzheimer Disease: genetics
|2 MeSH
650 _ 2 |a Interleukin-1beta: biosynthesis
|2 MeSH
650 _ 2 |a Interleukin-1beta: metabolism
|2 MeSH
650 _ 2 |a Animals
|2 MeSH
650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a Signal Transduction
|2 MeSH
650 _ 2 |a Disease Models, Animal
|2 MeSH
650 _ 2 |a STAT1 Transcription Factor: metabolism
|2 MeSH
650 _ 2 |a Mice
|2 MeSH
650 _ 2 |a Receptor Protein-Tyrosine Kinases: metabolism
|2 MeSH
650 _ 2 |a Receptor Protein-Tyrosine Kinases: genetics
|2 MeSH
650 _ 2 |a Amyloid beta-Peptides: metabolism
|2 MeSH
650 _ 2 |a Inflammasomes: metabolism
|2 MeSH
650 _ 2 |a THP-1 Cells
|2 MeSH
650 _ 2 |a Proto-Oncogene Proteins: metabolism
|2 MeSH
650 _ 2 |a Phosphorylation
|2 MeSH
650 _ 2 |a Axl Receptor Tyrosine Kinase
|2 MeSH
650 _ 2 |a Male
|2 MeSH
650 _ 2 |a Mice, Inbred C57BL
|2 MeSH
650 _ 2 |a Nitriles
|2 MeSH
650 _ 2 |a Mice, Transgenic
|2 MeSH
700 1 _ |a Brosseron, Frederic
|0 P:(DE-2719)2810593
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700 1 _ |a McManus, Róisín M
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700 1 _ |a Ising, Christina
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700 1 _ |a Görgen, Simon
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700 1 _ |a Schmidt, Susanne V
|b 5
700 1 _ |a Santarelli, Fracesco
|b 6
700 1 _ |a Lee, Se Young
|b 7
700 1 _ |a Jung, Hyuncheol
|b 8
700 1 _ |a Chung, Won-Suk
|b 9
700 1 _ |a Kim, Chan Hyuk
|b 10
700 1 _ |a Ruiz Laza, Agustín
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700 1 _ |a Ruiz de Almodóvar, Carmen
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700 1 _ |a Ramirez, Alfredo
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700 1 _ |a Latz, Eicke
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700 1 _ |a Heneka, Michael T
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773 _ _ |a 10.1093/jleuko/qiaf157
|g Vol. 117, no. 12, p. qiaf157
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