TREM2-mediated regulation of microglial activity: a promising target for the treatment of ischemic stroke

J Transl Med. 2025 Jul 11;23(1):782. doi: 10.1186/s12967-025-06799-3.

Abstract

Ischemic stroke, the most prevalent type of stroke globally, poses significant challenges due to its high incidence, morbidity, and long-term disability. Microglia, the resident immune cells of the central nervous system (CNS), play a dual role in the context of ischemic stroke. While they contribute to neuroinflammation by releasing pro-inflammatory cytokines and exacerbating neuronal injury, they also facilitate tissue repair, angiogenesis, and restoration of the blood-brain barrier (BBB) integrity through the secretion of anti-inflammatory and neurotrophic factors. Triggering receptor expressed on myeloid cells 2 (TREM2), predominantly expressed on microglia, is a critical regulator of microglial proliferation, survival, phagocytosis, polarization, inflammation, and metabolism. TREM2 has emerged as a key modulator of immune responses in ischemic stroke. This review provides a comprehensive examination of the multifaceted roles of TREM2 in microglial biology during ischemic stroke, integrating current insights into its molecular mechanisms. Furthermore, it highlights TREM2's potential as a transformative therapeutic target, advancing our understanding of neuroimmune regulation and promoting recovery after stroke.

Keywords: Ischemic stroke; Microglia; Neuroinflammation; Therapeutic target; Triggering receptor expressed on myeloid cells 2 (TREM2).

Publication types

  • Review

MeSH terms

  • Animals
  • Humans
  • Ischemic Stroke* / metabolism
  • Ischemic Stroke* / pathology
  • Ischemic Stroke* / therapy
  • Membrane Glycoproteins* / metabolism
  • Microglia* / metabolism
  • Microglia* / pathology
  • Molecular Targeted Therapy*
  • Receptors, Immunologic* / metabolism

Substances

  • Receptors, Immunologic
  • Membrane Glycoproteins
  • TREM2 protein, human