About TREM / Triggering Receptor Expressed on Myeloid Cells:
Triggering Receptor Expressed on Myeloid Cells protein (TREM) is a cell surface receptor primarily expressed by myeloid lineage cells, including microglia in the central nervous system. TREM is involved in phagocytosis and cytokine secretion in antigen-presenting cells, but its role in neurons remains unclear. However, TREM is often reported in neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, and multiple sclerosis.
Bone morphogenetic proteins (BMPs) are a group of cytokines that regulate neuronal differentiation in the brain. BMP2 has been found to strongly upregulate TREM expression in neurons in vitro in contrast with other BMPs, which show no effect. The same phenomenon was observed in microglia where TREM expression was upregulated after BMP2 treatment, suggesting an indirect role for microglia-mediated astrocyte activation.
Triggering Receptor Expressed on Myeloid Cells Function
TREM's main function is the phagocytosis of apoptotic neurons during development and regeneration. In Alzheimer's disease, microglia carry out a phagocytic activity against the amyloid-β peptide (Aβ), a cleavage product of APP, which accumulates in senile plaques in Alzheimer's patients. TREM expression has been shown to be negatively correlated with Aβ plaque load, suggesting it may play a role in Aβ phagocytosis.
TREM's structure consists of an N-terminal V-type immunoglobulin (Ig) domain, a short membrane-proximal region, and a C-terminal transmembrane, and a cytoplasmic domain. The Ig domain is homologous to the V region of immunoglobulin heavy chains and is involved in protein-protein interactions. It has been shown that TREM is able to bind BMPs in the membrane-proximal region. It is likely that this domain also mediates protein: protein interactions with other TREM ligands, although none have yet been identified. The cytoplasmic tail contains conserved motifs which are responsible for endocytosis and signal transduction to downstream molecules.