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Defective phagocytosis leads to neurodegeneration through systemic increased innate immune signaling.
Elguero, Johnny E; Liu, Guangmei; Tiemeyer, Katherine; Bandyadka, Shruthi; Gandevia, Heena; Duro, Lauren; Yan, Zhenhao; McCall, Kimberly.
Afiliación
  • Elguero JE; Department of Biology, Boston University, 5 Cummington Mall, Boston, MA 02115, USA.
  • Liu G; Department of Biology, Boston University, 5 Cummington Mall, Boston, MA 02115, USA.
  • Tiemeyer K; Department of Biology, Boston University, 5 Cummington Mall, Boston, MA 02115, USA.
  • Bandyadka S; Department of Biology, Boston University, 5 Cummington Mall, Boston, MA 02115, USA.
  • Gandevia H; Department of Biology, Boston University, 5 Cummington Mall, Boston, MA 02115, USA.
  • Duro L; Department of Biology, Boston University, 5 Cummington Mall, Boston, MA 02115, USA.
  • Yan Z; Department of Biology, Boston University, 5 Cummington Mall, Boston, MA 02115, USA.
  • McCall K; Department of Biology, Boston University, 5 Cummington Mall, Boston, MA 02115, USA.
iScience ; 26(10): 108052, 2023 Oct 20.
Article en En | MEDLINE | ID: mdl-37854687
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.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Idioma: En Revista: IScience Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Idioma: En Revista: IScience Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos