Table 1.
The similarities and differences between TREM-1 and TREM-2 in CNS diseases
| Similarity | Difference | ||
|---|---|---|---|
| TREM-1 | TREM-2 | ||
| Structure |
Composed of three parts: the extracellular immunoglobulin-like domain, the transmembrane domain and the cytoplasmic domain Two subtypes exist: the membrane-bound type and the soluble type [3–5] |
Enzyme: MMPs | Enzyme: ADAM 10 and ADAM 17 [5] |
| Ligands | PAMPs? DAMPs? (still unclear) [6, 7] | HMGB1, HSP70, CD177, actin, PGLYRP1, eCIRP(see “ligands” section) | Cellular debris, lipids, Aβ, nucleic acids, ApoE, LDL [5, 7–9] |
| Signaling Pathways | The transmembrane domain undergoes signaling by binding to DAP12 containing the ITAM. ITAM is phosphorylated by Src-family kinase, and recruits Syk to trigger downstream signaling cascades, including PI3K/Akt and MEK/ERK [3–5] |
Promote inflammation: JAK-STAT3/5, MEK/ERK, PI3K/Akt, NF-κB [6, 128]; Inhibit apoptosis: PI3K/Akt [6]; Promote pyroptosis: NLRP3/caspase-1 [84, 85, 100]; Induce oxidative stress: ROS [84, 127]; Interact with the TLR4 pathway to enhance inflammation [28, 94] |
Except DAP12, TREM-2 can also bind to DAP10 [5]; Promote phagocytosis and actin cytoskeleton rearrangement: VAV2/3-Rac1/Cdc42-Arp2/3 [7]; Promote cell growth: Pyk2/β-catenin [7]; Inhibit inflammation: Inhibit NF-κB and MEK/ERK [7, 10]; Inhibit Autophagy: PI3K/Akt-mTOR [11]; |