Inhibiting mtDNA-STING-NLRP3/IL-1β axis-mediated neutrophil infiltration protects neurons in Alzheimer's disease
© 2023 The Authors. Cell Proliferation published by Beijing Institute for Stem Cell and Regenerative Medicine and John Wiley & Sons Ltd..
Neutrophil is a pathophysiological character in Alzheimer's disease. The pathogen for neutrophil activation in cerebral tissue is the accumulated amyloid protein. In our present study, neutrophils infiltrate into the cerebra in two models (transgenic model APP/PS1 and stereotactic injection model) and promote neuron apoptosis, releasing their cellular constituents, including mitochondria and mitochondrial DNA (mtDNA). We found that both Aβ1-42 and mtDNA could provoke neutrophil infiltration into the cerebra, and they had synergistic effects when they presented together. This neutrophillic neuroinflammation upregulates expressions of STING, NLRP3 and IL-1β. These inflammatory cytokines with mtDNA constitute the mtDNA-STING-NLRP3/IL-1β axis, which is the prerequisite for neutrophil infiltration. When any factor in this pathway is depleted, the migration of neutrophils into cerebral tissue is ceased, with neurons and cognitive function being protected. Thus, we provide a novel perspective to alleviate the progression of Alzheimer's disease.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:57 |
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| Enthalten in: |
Cell proliferation - 57(2024), 1 vom: 08. Jan., Seite e13529 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Xia, Xiangyu [VerfasserIn] |
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| Links: |
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| Themen: |
Amyloid beta-Peptides |
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| Anmerkungen: |
Date Completed 08.01.2024 Date Revised 08.01.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1111/cpr.13529 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a © 2023 The Authors. Cell Proliferation published by Beijing Institute for Stem Cell and Regenerative Medicine and John Wiley & Sons Ltd. | ||
| 520 | |a Neutrophil is a pathophysiological character in Alzheimer's disease. The pathogen for neutrophil activation in cerebral tissue is the accumulated amyloid protein. In our present study, neutrophils infiltrate into the cerebra in two models (transgenic model APP/PS1 and stereotactic injection model) and promote neuron apoptosis, releasing their cellular constituents, including mitochondria and mitochondrial DNA (mtDNA). We found that both Aβ1-42 and mtDNA could provoke neutrophil infiltration into the cerebra, and they had synergistic effects when they presented together. This neutrophillic neuroinflammation upregulates expressions of STING, NLRP3 and IL-1β. These inflammatory cytokines with mtDNA constitute the mtDNA-STING-NLRP3/IL-1β axis, which is the prerequisite for neutrophil infiltration. When any factor in this pathway is depleted, the migration of neutrophils into cerebral tissue is ceased, with neurons and cognitive function being protected. Thus, we provide a novel perspective to alleviate the progression of Alzheimer's disease | ||
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| 700 | 1 | |a Zhao, Tingmei |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Jingyun |e verfasserin |4 aut | |
| 700 | 1 | |a Bi, Zhenfei |e verfasserin |4 aut | |
| 700 | 1 | |a Fu, Qianmei |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Jian |e verfasserin |4 aut | |
| 700 | 1 | |a Ao, Danyi |e verfasserin |4 aut | |
| 700 | 1 | |a Wei, Yuquan |e verfasserin |4 aut | |
| 700 | 1 | |a Wei, Xiawei |e verfasserin |4 aut | |
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