TREM2 in CNS homeostasis and neurodegenerative disease

Meghan M. Painter, Yuka Atagi, Chia-Chen Liu, Rosa V Rademakers, Huaxi Xu, John D. Fryer, Guojun D Bu

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

Myeloid-lineage cells accomplish a myriad of homeostatic tasks including the recognition of pathogens, regulation of the inflammatory milieu, and mediation of tissue repair and regeneration. The innate immune receptor and its adaptor protein - triggering receptor expressed on myeloid cells 2 (TREM2) and DNAX-activating protein of 12 kDa (DAP12) - possess the ability to modulate critical cellular functions via crosstalk with diverse signaling pathways. As such, mutations in TREM2 and DAP12 have been found to be associated with a range of disease phenotypes. In particular, mutations in TREM2 increase the risk for Alzheimer's disease and other neurodegenerative disorders. The leading hypothesis is that microglia, the resident immune cells of the central nervous system, are the major myeloid cells affected by dysregulated TREM2-DAP12 function. Here, we review how impaired signaling by the TREM2-DAP12 pathway leads to altered immune responses in phagocytosis, cytokine production, and microglial proliferation and survival, thus contributing to disease pathogenesis.

Original languageEnglish (US)
Article number43
JournalMolecular Neurodegeneration
Volume10
Issue number1
DOIs
StatePublished - Sep 4 2015

Fingerprint

Central Nervous System Diseases
Myeloid Cells
Neurodegenerative Diseases
Homeostasis
Proteins
Mutation
Aptitude
Microglia
Phagocytosis
Regeneration
Alzheimer Disease
Central Nervous System
Cytokines
Phenotype

Keywords

  • Alzheimer's disease
  • Inflammation
  • Microglia
  • TREM2

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Clinical Neurology
  • Molecular Biology

Cite this

TREM2 in CNS homeostasis and neurodegenerative disease. / Painter, Meghan M.; Atagi, Yuka; Liu, Chia-Chen; Rademakers, Rosa V; Xu, Huaxi; Fryer, John D.; Bu, Guojun D.

In: Molecular Neurodegeneration, Vol. 10, No. 1, 43, 04.09.2015.

Research output: Contribution to journalArticle

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AU - Bu, Guojun D

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