TREM2 is a member of the immunoglobulin superfamily. Endogenous ligands of this receptor are unknown but when triggered, it signals through the transmembrane adapter protein TYROBP/DAP12 to activate phagocytosis of pathogens and cellular debris.

Feeding the small molecule agonist to cynomolgus macaques triggered a dramatic drop in levels of soluble TREM2 in their CSF over the first 24 hours, followed by a return to baseline levels three days later. Glue That TREM2. Vigil’s small-molecule TREM2 agonists promote clustering and signaling through the full-length receptor (left).

TREM2 encodes Triggering Receptor Expressed on Myeloid Cells 2, a transmembrane receptor that modulates microglial activity and survival. TREM2 variants cause Nasu-Hakola disease (NHD), a rare autosomal recessive early-onset dementia, and may modify the risk of developing Alzheimer’s disease (AD), frontotemporal dementia (FTD), Parkinson’s ...

Jan 23, 2023 · As seen by SPECT imaging, much more ATV:TREM2 flooded the mouse brain (right) after intravenous injection than anti-TREM2 without the antibody transport vehicle (left). [Courtesy of van Lengerich et al., Nature Neuroscience, 2023.] ATV:TREM2 increased the number of proliferating microglia as measured by uptake of the modified nucleoside EdU.

Feb 7, 2018 · TREM2 is associated with the risk of Alzheimer's disease in Spanish population. Neurobiol Aging. 2013 Jun;34(6):1711.e15-7. Epub 2013 Feb 5 PubMed. Finelli D, Rollinson S, Harris J, Jones M, Richardson A, Gerhard A, Snowden J, Mann D, Pickering-Brown S. TREM2 analysis and increased risk of Alzheimer's disease. Neurobiol Aging. 2015 Jan;36(1 ...

Mar 13, 2018 · The TREM2 knockout microglia poorly phagocytosed beads in culture, while BAC-TREM2 mice ate voraciously, in agreement with previous studies suggesting that TREM2 stimulates phagocytosis (Jul 2016 news). “Our interpretation is that TREM2 reprograms microglia, making them more efficient at removing or walling off plaques,” Yang told Alzforum.

Aug 31, 2017 · Thinking that limiting ectodomain shedding might improve TREM2 signaling (see image below), the three research groups set out to find the cleavage site. Snip Site. ADAM10, or other proteases, may shed TREM2’s extracellular ligand binding domain, abolishing TREM2-mediated signaling. (Courtesy of Yeh et al., 2017, Trends Mol Med.)

Jul 14, 2020 · Availability: TREM2 mice are available through Marco Colonna. Summary. This mouse model, referred to here as TREM2 CV, expresses the common variant of human TREM2 in the absence of mouse Trem2. Transgenic TREM2 is expressed in microglia and macrophages, where it was shown to function properly in an ex vivo assay.

Jul 29, 2021 · After TREM2 ASO treatment (bottom), plaques are sparse and microglia (green) more ramified, indicating a resting state. [Courtesy of Schoch et al., PNAS.] TREM2 orchestrates microglial responses, boosting survival and phagocytosis to protect the damaged brain (Feb 2015 news; Jul 2016 news; Apr 2017 conference news). It also prods microglia to ...

Mar 17, 2022 · TREM2 is a cell surface receptor of the immunoglobulin superfamily that is expressed exclusively in the myeloid lineage cells, particularly microglia in the central nervous system. Engagement of TREM2 by ligands, such as lipoproteins or Aβ, initiates signaling through its adaptors DAP12 or DAP10 to trigger downstream signaling pathways.