Role of TREM2 in neuroinflammation regulation: mechanisms, disease associations, and therapeutic translation advances
Year: 2025
Type: article
Abstract: BACKGROUND: Neuroinflammation underlies the pathogenesis of neurodegenerative diseases, CNS trauma, aging, and pain disorders, profoundly influencing disease progression and clinical outcomes. TREM2 is an innate immune transmembrane receptor predominantly expressed on microglia in the CNS, primarily for sensing tissue damage and coordinating immune remodeling. MAIN BODY: TREM2, by binding to its ligands and subsequently activating DAP12/10-mediated signaling pathways, coordinates microglial phagocytosis, metabolism, phenotype polarization, and inflammatory responses, thereby regulating neuroinflammation in various neurological diseases. Contrary to the conventional view of its neuroinflammatory suppression and neuroprotection, growing evidence has suggested that TREM2 exhibits dual functional roles that correlate with disease context and stage. This review provides a detailed overview of TREM2, including its structural features and relevant ligands, and elucidates the pathological mechanisms underlying TREM2-mediated regulation at both molecular and disease-specific levels—with particular focus on its effects on neuroinflammation through the modulation of microglial function. Finally, this review also discusses the current advances in TREM2-oriented therapeutic strategies and clinical translation, highlighting their potential applications for neuroinflammatory diseases. CONCLUSIONS: TREM2 acts as a central regulator of neuroinflammation by modulating microglial function, exhibiting context-dependent neuroprotective or pathological roles across neurological disorders. Current TREM2-targeted therapies show translational potential for neuroinflammatory diseases, while sTREM2 holds value as a clinical biomarker.
Authors: Yinsheng Liao, Guo Mu, Shengfeng Deng, Bin Lu, Maoyao Zheng
Institution: Zigong First People's Hospital
Language: English
Subfield: Neurology
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,890
OpenAlex ID: W7117328126