ArticleJournal of neuroinflammation2016
Functional involvement of γ-secretase in signaling of the triggering receptor expressed on myeloid cells-2 (TREM2).
Article in Journal of neuroinflammation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 43 citations in OpenAlex.
- The γ-secretase complex: from discovery to a therapeutic target.RSC chemical biology · 2026Review
- Soluble TREM2 Is Elevated in Pediatric Patients with Anti-NMDAR Encephalitis.Journal of clinical medicine · 2026Article
- Parkinson's disease: spatiotemporal regulation and therapeutic prospects of TREM2-mediated microglial responses.NPJ Parkinson's disease · 2026Review
- TREM2 and microglial immunity in Alzheimer's disease: mechanisms, genetics, and therapeutic opportunities.Frontiers in immunology · 2026Review
- Roles of TREM2 in Alzheimer's disease.Translational neurodegeneration · 2025Review
- Is TREM2 a Stretch: Implications of TREM2 Along Spinal Cord Circuits in Health, Aging, Injury, and Disease.Cells · 2025Review
- Endogenous γ-Secretase Is Linked to Phagocytic Activity in Microglial Cells.Sensors (Basel, Switzerland) · 2025Article
- DAP12 interacts with RER1 and is retained in the secretory pathway before assembly with TREM2.Cellular and molecular life sciences : CMLS · 2024Article
- Presenilin Deficiency Results in Cellular Cholesterol Accumulation by Impairment of Protein Glycosylation and NPC1 Function.International journal of molecular sciences · 2024Article
- Autosomal Dominant Alzheimer's Disease Mutations in Human Microglia Are Not Sufficient to Trigger Amyloid Pathology in WT Mice but Might Affect Pathology in 5XFAD Mice.International journal of molecular sciences · 2024Article
- Decoding sTREM2: its impact on Alzheimer's disease - a comprehensive review of mechanisms and implications.Frontiers in aging neuroscience · 2024Review
- γ-Secretase fanning the fire of innate immunity.Biochemical Society transactions · 2023Review
- Modifiable Innate Biology within the Gut-Brain Axis for Alzheimer's Disease.Biomedicines · 2022Review
- Reduced TREM2 activation in microglia of patients with Alzheimer's disease.FEBS open bio · 2021Article
- TREM2 modulates differential deposition of modified and non-modified Aβ species in extracellular plaques and intraneuronal deposits.Acta neuropathologica communications · 2021Article
- TREM2 ectodomain and its soluble form in Alzheimer's disease.Journal of neuroinflammation · 2020Review
- Importance of γ-secretase in the regulation of liver X receptor and cellular lipid metabolism.Life science alliance · 2020Article
- Early-Onset Familial Alzheimer Disease Variant PSEN2 N141I Heterozygosity is Associated with Altered Microglia Phenotype.Journal of Alzheimer's disease : JAD · 2020Article
- Immune Signaling in Neurodegeneration.Immunity · 2019Review
- Atherogenic LOX-1 signaling is controlled by SPPL2-mediated intramembrane proteolysis.The Journal of experimental medicine · 2019Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundTriggering receptor expressed on myeloid cells-2 (TREM2) exerts important functions in the regulation of monocytes, like dendritic cells, osteoclasts, tissue macrophages, and microglia. Mutations in TREM2 are associated with several diseases, including Nasu-Hakola disease, frontotemporal dementia, and Alzheimer's disease (AD). TREM2 undergoes sequential proteolytic processing by ectodomain shedding and intramembrane proteolysis.
findingsWe show that inhibition of γ-secretase-dependent cleavage of the TREM2 C-terminal fragment in cellular membranes interferes with TREM2-dependent signaling and cellular function. Inhibition of γ-secretase decreases membrane-proximal signaling and intracellular Ca(2+) response. Decreased signaling alters morphological changes and phagocytic activity of cells upon selective stimulation of TREM2.
conclusionsThe data demonstrate the importance of γ-secretase-dependent intramembrane processing in TREM2-mediated signaling and, thus, a functional relation of two AD-associated proteins.
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