The Triggering Receptor Expressed on Myeloid Cells 2: A Molecular Link of Neuroinflammation and Neurodegenerative Diseases

J Biol Chem. 2016 Feb 26;291(9):4334-41. doi: 10.1074/jbc.R115.704981. Epub 2015 Dec 22.

Abstract

The triggering receptor expressed on myeloid cells (TREM) 2 is a member of the immunoglobulin superfamily of receptors and mediates signaling in immune cells via engagement of its co-receptor DNAX-activating protein of 12 kDa (DAP12). Homozygous mutations in TREM2 or DAP12 cause Nasu-Hakola disease, which is characterized by bone abnormalities and dementia. Recently, a variant of TREM2 has also been associated with an increased risk for Alzheimer disease. The selective expression of TREM2 on immune cells and its association with different forms of dementia indicate a contribution of this receptor in common pathways of neurodegeneration.

Keywords: Alzheimer disease; cell signaling; microglia; neurodegenerative disease; neuroinflammation; protein processing.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism
  • Animals
  • Humans
  • Lipodystrophy / genetics
  • Lipodystrophy / immunology
  • Lipodystrophy / metabolism
  • Lipodystrophy / pathology
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism*
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Microglia / immunology
  • Microglia / metabolism
  • Microglia / pathology
  • Models, Biological*
  • Mutation
  • Myeloid Cells / immunology
  • Myeloid Cells / metabolism*
  • Myeloid Cells / pathology
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Neurodegenerative Diseases / genetics
  • Neurodegenerative Diseases / immunology
  • Neurodegenerative Diseases / metabolism*
  • Neurodegenerative Diseases / pathology
  • Neurons / immunology
  • Neurons / metabolism*
  • Neurons / pathology
  • Osteochondrodysplasias / genetics
  • Osteochondrodysplasias / immunology
  • Osteochondrodysplasias / metabolism
  • Osteochondrodysplasias / pathology
  • Receptors, Immunologic / genetics
  • Receptors, Immunologic / metabolism*
  • Subacute Sclerosing Panencephalitis / genetics
  • Subacute Sclerosing Panencephalitis / immunology
  • Subacute Sclerosing Panencephalitis / metabolism
  • Subacute Sclerosing Panencephalitis / pathology
  • Triggering Receptor Expressed on Myeloid Cells-1

Substances

  • Adaptor Proteins, Signal Transducing
  • Membrane Glycoproteins
  • Membrane Proteins
  • Nerve Tissue Proteins
  • Receptors, Immunologic
  • TREM1 protein, human
  • TREM2 protein, human
  • TYROBP protein, human
  • Triggering Receptor Expressed on Myeloid Cells-1

Supplementary concepts

  • Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy