{{Infobox
| image = TREM2 Structure
| infobox-header = TREM2 Protein
| infobox-subheader = Triggering Receptor Expressed on Myeloid Cells 2
| label1 = Gene
| data1 = TREM2
| label2 = UniProt ID
| data2 = Q9NZC2
| label3 = PDB Structures
| data2 = 5W5F, 5W5X, 6VWX
| label4 = Molecular Weight
| data4 = ~35 kDa (soluble form)
| label5 = Subcellular Localization
| data5 = Cell membrane (type I transmembrane protein); also shed as soluble TREM2 (sTREM2)
| label6 = Protein Family
| data6 = Immunoglobulin superfamily, TREM family
| label7 = Expression
| data7 = Primarily on microglia in the CNS; also on macrophages, dendritic cells, and osteoclasts
}}
Trem2 Protein is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
TREM2 is a gene/protein encoding a key neuronal protein involved in synaptic function, signal transduction, and cellular homeostasis. Dysfunction of TREM2 is associated with neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, and related disorders.
TREM2 is a type I transmembrane protein consisting of:
The protein undergoes proteolytic cleavage, releasing a soluble form (sTREM2) that can be detected in cerebrospinal fluid. The sTREM2/CSF TREM2 ratio is being investigated as a biomarker for microglial activity.
TREM2 is a receptor that plays a critical role in microglial function:
| Approach | Status | Description |
|---|---|---|
| Agonistic antibodies | Preclinical | Anti-TREM2 antibodies to activate receptor signaling |
| TREM2 ectodomain | Research | soluble TREM2 as therapeutic agent |
| Gene therapy | Research | Viral vector delivery of functional TREM2 |
| Small molecules | Discovery | TREM2-binding compounds to enhance function |
The study of Trem2 Protein has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
Rare variants in TREM2 greatly increase AD risk[1]:
These variants impair microglial function and the brain's ability to clear amyloid plaques.
TREM2 activates critical microglial functions[2]:
TREM2 is required for the DAM response:
Several approaches are in development[3]:
TREM2 pairs with DAP12 adapter protein:
TREM2 modulates microglial phenotypes:
Jonsson T, et al. (2013). Variant of TREM2 associated with the risk of Alzheimer's disease. N Engl J Med, 368(2):107-116. ↩︎
Ulland TK, Colonna M. (2018). TREM2 — a key player in microglial biology and Alzheimer disease. Nat Rev Neurol, 14(11):667-675. ↩︎
Price BR, et al. (2020). Therapeutic approaches to target TREM2 in Alzheimer's disease. J Neuroinflammation, 17(1):341. ↩︎