Non-pathological roles of microglial TREM2/DAP12: TREM2/DAP12 regulates the physiological functions of microglia from
Hiroyuki Konishi1, Hiroshi Kiyama1
1Department of Functional Anatomy and Neuroscience, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan.
Abstract:
Triggering receptor expressed on myeloid cells 2 (TREM2) forms a receptor complex with DNAX-activating protein of 12 kDa (DAP12) on the microglial plasma membrane. A wide variety of protein and non-protein ligands, including lipids and DNA, can bind to TREM2, inducing the activation of microglia via DAP12. Both Trem2 and Dap12 have been identified as causative genes for Nasu-Hakola disease, which causes presenile dementia in association with bone cysts. Furthermore, TREM2/DAP12 signaling represents an essential inducer of the activated microglial phenotype in neuronal diseases, including Alzheimer's disease. Therefore, most previous studies examining TREM2/DAP12 have focused on their roles in microglia under pathological conditions. However, a growing body of evidence has demonstrated the involvement of TREM2/DAP12 signaling in the regulation of physiological functions in microglia. Accordingly, by examining the importance of TREM2/DAP12 in the regulation of microglial activity during development, homeostasis, and aging in the brain, this review elucidates the roles played by this complex in the healthy brain.
Insights
Triggering receptor expressed on myeloid cells 2 (TREM2) and DAP12 signaling are crucial for microglial function. This review explores their roles in the healthy brain during development, homeostasis, and aging.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- The TREM2/DAP12 complex is vital for microglial function.
- TREM2 binds diverse ligands, activating microglia via DAP12.
- Mutations in TREM2/DAP12 cause Nasu-Hakola disease, a form of dementia.
Purpose of the Study:
- To review the role of TREM2/DAP12 signaling in microglia.
- To elucidate the function of TREM2/DAP12 in the healthy brain.
- To examine TREM2/DAP12's role during brain development, homeostasis, and aging.
Main Methods:
- Literature review of studies on TREM2/DAP12 signaling.
- Analysis of TREM2/DAP12 involvement in microglial physiology.
- Synthesis of findings on TREM2/DAP12 in neurodevelopment, aging, and homeostasis.
Main Results:
- TREM2/DAP12 signaling is implicated in microglial activation in neurological diseases.
- Evidence suggests TREM2/DAP12 signaling regulates physiological microglial functions.
- The complex plays a role in microglial activity across the lifespan.
Conclusions:
- TREM2/DAP12 signaling is essential for microglial activity beyond disease states.
- Understanding TREM2/DAP12 in the healthy brain is critical for neurological health.
- This review highlights the complex's importance in normal brain function and aging.
