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- W4313408053 abstract "Abstract The phagocytosis of apoptotic cells and cellular debris by microglia critically regulates immune homeostasis in the brain. In Alzheimer’s Disease (AD), microglial phagocytosis of amyloid-β (Aβ) aggregates is thought to play a protective role in AD pathogenesis, but the mechanisms by which this occurs are not well understood. Recent work has suggested that phosphatidylserine (PtdSer)-sensing receptors may induce Aβ plaque engulfment, and data from our lab and others’ supports this idea. To better understand the role of PtdSer-sensing receptors in Aβ clearance, we utilized immortalized cell lines and isolated primary microglia to examine PtdSer-mediated phagocytosis of Aβ aggregate targets in vitro and compared this to phagocytosis of apoptotic cells, as well as to phagocytosis by Fcγ receptors and complement receptors. Phagocytosis was measured by live-cell imaging and flow cytometry, and revealed distinct kinetics between the different forms of phagocytosis. We further investigated the role of specific PtdSer receptors using genetic and pharmacologic blocking approaches. In vivo results using the APP/PS1 AD mouse model support a role for the PtdSer binding protein Gas6 in mediating Aβ plaque clearance. Our work supports a model in which the effective clearance of Aβ by microglia occurs via a combination of phagocytic mechanisms." @default.
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- W4313408053 date "2022-05-01" @default.
- W4313408053 modified "2023-09-26" @default.
- W4313408053 title "The role of phosphatidylserine receptor-mediated phagocytosis of amyloid-β by microglia in Alzheimer’s Disease." @default.
- W4313408053 doi "https://doi.org/10.4049/jimmunol.208.supp.163.14" @default.
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