TREM2 in Alzheimer's disease: Structure, function, therapeutic prospects, and activation challenges

Mol Cell Neurosci. 2024 Mar:128:103917. doi: 10.1016/j.mcn.2024.103917. Epub 2024 Jan 19.

Abstract

Triggering receptor expressed on myeloid cells 2 (TREM2) is a membrane glycoprotein that plays a crucial role in the regulation of microglial survival, activation, phagocytosis, as well as in the maintenance of brain homeostasis and the inflammatory response to injury or neurodegeneration. This review provides a comprehensive overview of TREM2 structure and functions, highlighting the role of its variants in the development and progression of Alzheimer's disease (AD), a devastating neurodegenerative disease that affects millions of people worldwide. Additionally, the article discusses the potential of TREM2 as a therapeutic target in AD, analyzing the current state of research and future prospects. Given the significant challenges associated with the activation of TREM2, particularly due to its diverse isoforms and the delicate balance required to modulate the immune response without triggering hyperactivation, this review aims to enhance our understanding of TREM2 in AD and inspire further research into this promising yet challenging therapeutic target.

Keywords: Alzheimer's disease; Amyloid plaques; Microglia; Phagocytosis; TREM2.

Publication types

  • Review

MeSH terms

  • Alzheimer Disease* / therapy
  • Amyloid beta-Peptides
  • Brain / metabolism
  • Humans
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism
  • Microglia / metabolism
  • Neurodegenerative Diseases*
  • Receptors, Immunologic / genetics

Substances

  • Membrane Glycoproteins
  • Amyloid beta-Peptides
  • TREM2 protein, human
  • Receptors, Immunologic