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Open Access 01-12-2015 | Review

TREM2 in CNS homeostasis and neurodegenerative disease

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

Published in: Molecular Neurodegeneration | Issue 1/2015

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.

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Title: TREM2 in CNS homeostasis and neurodegenerative disease
Authors: Meghan M. Painter
Yuka Atagi
Chia-Chen Liu
Rosa Rademakers
Huaxi Xu
John D. Fryer
Guojun Bu
Publication date: 01-12-2015
Publisher: BioMed Central
Published in: Molecular Neurodegeneration / Issue 1/2015
Electronic ISSN: 1750-1326
DOI: https://doi.org/10.1186/s13024-015-0040-9

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TREM2 in CNS homeostasis and neurodegenerative disease

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