AI Article Synopsis
- - Niemann-Pick disease Type C (NPC) is a neurodegenerative disorder caused by mutations in the NPC1 gene, resulting in cholesterol buildup in cells, particularly affecting microglial function.
- - In neonatal Npc1 mutant mice, researchers observed reactive microglia with increased CD68 and phagocytic activity, indicating disrupted TREM2-mTOR signaling pathways.
- - The study found that deleting the Trem2 gene in Npc1-deficient BV2 cells partially restored microglial function, suggesting that NPC1 loss alters microglial morphology and lysosomal function via TREM2-mTOR signaling.
Article Abstract
Niemann-Pick disease Type C (NPC) is a neurodegenerative disease mainly caused by the mutation in NPC1 gene, leading to massive accumulation of unesterified cholesterol in the late endosome/lysosome of cells. Impaired phenotype of microglia is a hallmark in Npc1 mutant mice (Npc1 mice). However, the mechanism of Npc1 in regulating microglial function is still unclear. Here, we showed that the reactive microglia in the neonatal Npc1 mice indicated by the increased lysosome protein CD68 and phagocytic activity were associated with disrupted TREM2-mTOR signaling in microglia. Furthermore, in Npc1-deficient BV2 cells, genetic deletion of Trem2 partially restored microglial function, probably via restored mTOR signaling. Taken together, our findings indicated that loss of Npc1 in microglia caused changes of their morphologies and the impairment of lysosomal function, which were linked to the TREM2-mTOR signaling pathway.
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| http://dx.doi.org/10.1016/j.bbadis.2024.167478 | DOI Listing |
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