ArticleCell reports2025
Neuraminidase 1 regulates neuropathogenesis by governing the cellular state of microglia via modulation of Trem2 sialylation.
Article in Cell reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed.
- Glycosylation in gut-brain communication: from the intestinal barrier and microbiota to immune and neural signaling.Gut microbes · 2026Review
- Single-cell RNA sequencing reveals the interaction of TREM2Immunologic research · 2026Article
- Calcineurin/NFAT signaling in the temporal integration of Ca²⁺ stress in neurodegeneration.Cell death discovery · 2026Review
- A model of free sialic acid storage disorder reveals hypomyelinating leukodystrophy and Purkinje cell degeneration.Disease models & mechanisms · 2026Article
- Review
- Sialylation in the nervous system: Functions and mechanisms.The Journal of biological chemistry · 2026Review
- Decoding TREM2 Signaling Pathways: Linking Macrophage Glycolysis to Inflammatory Diseases in the CNS.Neurology(R) neuroimmunology & neuroinflammation · 2026Review
- Alterations in secondary lipids are associated with neuroinflammation in the brain of Neu1-deficient mice.Cell and tissue research · 2026Article
- Nutritional substrates and microglial metabolic fitness in brain aging and Alzheimer's disease: from lipid handling to TREM2-linked translation.Frontiers in nutrition · 2026Review
- Decoding sialidase: physiological roles, pathological pathways, and clinical opportunities.Frontiers in cellular and infection microbiology · 2026Review
- Epididymal epithelial cells facilitate NEU1 loading to modulate sperm α-2,6 sialylation, enhance maturation and motility.Cellular and molecular life sciences : CMLS · 2025Article
- Prognostic and immunological implications of sialylation-associated gene signatures in hepatocellular carcinoma.Annals of medicine · 2025Article
- TREM2-mediated regulation of myeloid cells in the tumor microenvironment: new insights and therapeutic prospects.NPJ precision oncology · 2025Review
- Roles of TREM2 in Alzheimer's disease.Translational neurodegeneration · 2025Review
- Sialidases as Potential Therapeutic Targets for Treatment of a Number of Human Diseases.International journal of molecular sciences · 2025Review
- NEU1-Mediated Extracellular Vesicle Glycosylation in Alzheimer's Disease: Mechanistic Insights into Intercellular Communication and Therapeutic Targeting.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Emerging Insights into Brain Inflammation: Stem-Cell-Based Approaches for Regenerative Medicine.International journal of molecular sciences · 2025Review
- Genetic Insights and Clinical Implications ofGenes · 2025Review
- Single-cell transcriptome-wide Mendelian randomization identifies mitochondrial targets in immune cells for Major Depressive Disorder.Frontiers in immunology · 2025Article
- Glial-mediated immune modulation in glaucomatous neurodegeneration: mechanisms and therapeutic implications.Frontiers in immunology · 2025Review
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6 authors.
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Abstract
Neuraminidase 1 (NEU1) cleaves terminal sialic acids from sialoglycoproteins in endolysosomes and at the plasma membrane. As such, NEU1 regulates immune cells, primarily those of the monocytic lineage. Here, we examine how Neu1 influences microglia by modulating the sialylation of full-length Trem2 (Trem2-FL), a multifunctional receptor that regulates microglial survival, phagocytosis, and cytokine production. When Neu1 is deficient/downregulated, Trem2-FL remains sialylated, accumulates intracellularly, and is excessively cleaved into a C-terminal fragment (Trem2-CTF) and an extracellular soluble domain (sTrem2), enhancing their signaling capacities. Sialylated Trem2-FL (Sia-Trem2-FL) does not hinder Trem2-FL-DAP12-Syk complex assembly but impairs signal transduction through Syk, ultimately abolishing Trem2-dependent phagocytosis. Concurrently, Trem2-CTF-DAP12 complexes dampen NF-κB signaling, while sTrem2 propagates Akt-dependent cell survival and NFAT1-mediated production of TNF-α and CCL3. Because NEU1 and Trem2 are implicated in neurodegenerative/neuroinflammatory diseases, including Alzheimer disease and sialidosis, modulating NEU1 activity represents a therapeutic approach to broadly regulate microglia-mediated neuroinflammation.
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