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Defective phagocytosis leads to neurodegeneration through systemic increased innate immune signaling.


ABSTRACT: In nervous system development, disease, and injury, neurons undergo programmed cell death, leaving behind cell corpses that are removed by phagocytic glia. Altered glial phagocytosis has been implicated in several neurological diseases including Alzheimer's disease. To untangle the links between glial phagocytosis and neurodegeneration, we investigated Drosophila mutants lacking the phagocytic receptor Draper. Loss of Draper leads to persistent neuronal cell corpses and age-dependent neurodegeneration. Here we investigate whether the phagocytic defects observed in draper mutants lead to chronic increased immune activation that promotes neurodegeneration. We found that the antimicrobial peptide Attacin-A is highly upregulated in the fat body of aged draper mutants and that the inhibition of the Immune deficiency (Imd) pathway in the glia and fat body of draper mutants led to reduced neurodegeneration. Taken together, these findings indicate that phagocytic defects lead to neurodegeneration via increased immune signaling, both systemically and locally in the brain.

SUBMITTER: Elguero JE 

PROVIDER: S-EPMC10579427 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature

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Defective phagocytosis leads to neurodegeneration through systemic increased innate immune signaling.

Elguero Johnny E JE   Liu Guangmei G   Tiemeyer Katherine K   Bandyadka Shruthi S   Gandevia Heena H   Duro Lauren L   Yan Zhenhao Z   McCall Kimberly K  

iScience 20230926 10


In nervous system development, disease, and injury, neurons undergo programmed cell death, leaving behind cell corpses that are removed by phagocytic glia. Altered glial phagocytosis has been implicated in several neurological diseases including Alzheimer's disease. To untangle the links between glial phagocytosis and neurodegeneration, we investigated <i>Drosophila</i> mutants lacking the phagocytic receptor Draper. Loss of Draper leads to persistent neuronal cell corpses and age-dependent neur  ...[more]

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