Affiliation:
1. Laboratory of Aging Research and Cancer Drug Target, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital Sichuan University Chengdu Sichuan China
Abstract
AbstractNeutrophil 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.
Funder
National Science Foundation
Subject
Cell Biology,General Medicine
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