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Microglial TREM2/DAP12 Signaling: A Double-Edged Sword in Neural Diseases

Hiroyuki Konishi1, Hiroshi Kiyama1

  • 1Department of Functional Anatomy and Neuroscience, Nagoya University Graduate School of Medicine, Nagoya University, Nagoya, Japan.

Frontiers in Cellular Neuroscience
|August 22, 2018
PubMed

Insights

Microglia activation via TREM2/DAP12 signaling shifts their state in neural diseases. This pathway has varied effects, offering potential for targeted therapies in conditions like Alzheimer's and Parkinson's disease.

Area of Science:

  • Neuroscience
  • Immunology
  • Cell Biology

Background:

  • Microglia, the central nervous system's immune cells, become activated during neuronal injury and neurodegenerative diseases, initiating neuroinflammation.
  • Microglial activation, influenced by timing and magnitude, critically determines neuronal fate, necessitating understanding of its molecular mechanisms for targeted therapies.
  • Plasma membrane receptors are key activators of microglia; this review focuses on the TREM2/DAP12 receptor complex.

Purpose of the Study:

  • To review the role of the TREM2/DAP12 receptor complex in microglial activation.
  • To explore how TREM2/DAP12 signaling influences microglial states in various neural diseases.
  • To discuss the dual beneficial and detrimental roles of TREM2/DAP12-mediated microglial activation across different disease contexts.

Main Methods:

  • Review of recent transcriptome approaches identifying TREM2/DAP12 signaling.
  • Analysis of animal model studies investigating TREM2/DAP12 functions in neural diseases.
  • Synthesis of current research on TREM2/DAP12's impact on microglial survival, phagocytosis, and cytokine production.

Main Results:

  • TREM2/DAP12 signaling is identified as a principal regulator transforming microglia from a homeostatic to a disease-associated state.
  • TREM2/DAP12 plays critical roles in microglial activity regulation across diverse neural conditions, including Alzheimer's, Parkinson's, and peripheral nerve injury.
  • The outcomes of TREM2/DAP12-mediated microglial activation can be either detrimental or beneficial, depending on the specific disease context.

Conclusions:

  • TREM2/DAP12 signaling is a central mechanism in microglial responses to neural injury and disease.
  • Understanding the context-dependent roles of TREM2/DAP12 is crucial for developing effective microglia-targeted therapies.
  • Further research into TREM2/DAP12 pathways may unlock new therapeutic strategies for a range of neurological disorders.
Keywords:
ITAMSykTYROBPdamagedegenerationinflammationinjuryregeneration

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