TREM2

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TREM2
Identifiers
Aliases TREM2, TREM-2, Trem2a, Trem2b, Trem2c, triggering receptor expressed on myeloid cells 2
External IDs MGI: 1913150 HomoloGene: 10352 GeneCards: TREM2
Genetically Related Diseases
Alzheimer's disease[1]
RNA expression pattern
PBB GE TREM2 219725 at fs.png
More reference expression data
Orthologs
Species Human Mouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001271821
NM_018965

NM_001272078
NM_031254

RefSeq (protein)

NP_001258750
NP_061838

NP_001259007.1
NP_112544.1
NP_001259007
NP_112544

Location (UCSC) Chr 6: 41.16 – 41.16 Mb Chr 17: 48.35 – 48.35 Mb
PubMed search [2] [3]
Wikidata
View/Edit Human View/Edit Mouse

Triggering receptor expressed on myeloid cells 2 also known as TREM-2 is a protein that in humans is encoded by the TREM2 gene.[4][5][6]

Function[edit]

Monocyte/macrophage- and neutrophil-mediated inflammatory responses can be stimulated through a variety of receptors, including G protein-linked 7-transmembrane receptors (e.g., FPR1), Fc receptors, CD14 and Toll-like receptors (e.g., TLR4), and cytokine receptors (e.g., IFNGR1). Engagement of these receptors can also prime myeloid cells to respond to other stimuli. Myeloid cells express receptors belonging to the Immunoglobulin (Ig) superfamily, such as TREM2, or to the C-type lectin superfamily. Depending on their transmembrane and cytoplasmic sequence structure, these receptors have either activating (e.g., KIR2DS1) or inhibitory functions (e.g., KIR2DL1).[6]

Clinical significance[edit]

Homozygous mutations in TREM2 are known to cause rare, autosomal recessive forms of dementia with an early onset and presenting with[5] or without[7] bone cysts and fractures.

A rare missense mutation (rs75932628-T) in the gene encoding TREM2, (predicted to result in an R47H substitution), confers a significant risk of Alzheimer's disease. Given the reported antiinflammatory role of TREM2 in the brain, it is suspected of interfering with the brain’s ability to prevent the buildup of plaque.[8][9] TREM2 mutations increase the risk of neurodegenerative conditions such as Alzheimer's disease, amyotrophic lateral sclerosis, and Parkinson's disease. TREM2 interacts with DAP12 in microglia to trigger phagocytosis of amyloid beta peptide and apoptotic neurons without inflammation. Mutations in TREM2 impair the normal proteolytic maturation of the protein which in turn interferes with phagocytosis and may therefore contribute to the pathogenesis of Alzheimer's disease.[10]

Soluble TREM2 has been detected in human cerebrospinal fluid (CSF), where it was found to be elevated in CSF of patients with multiple sclerosis and other inflammatory neurological conditions in comparison to patients without inflammatory neurologic disorders.[11]

References[edit]

  1. ^ "Diseases that are genetically associated with TREM2 view/edit references on wikidata". 
  2. ^ "Human PubMed Reference:". 
  3. ^ "Mouse PubMed Reference:". 
  4. ^ Bouchon A, Dietrich J, Colonna M (Jun 2000). "Cutting edge: inflammatory responses can be triggered by TREM-1, a novel receptor expressed on neutrophils and monocytes". J. Immunol. 164 (10): 4991–5. doi:10.4049/jimmunol.164.10.4991. PMID 10799849. 
  5. ^ a b Paloneva J, Manninen T, Christman G, Hovanes K, Mandelin J, Adolfsson R, Bianchin M, Bird T, Miranda R, Salmaggi A, Tranebjaerg L, Konttinen Y, Peltonen L (Aug 2002). "Mutations in two genes encoding different subunits of a receptor signaling complex result in an identical disease phenotype". Am. J. Hum. Genet. 71 (3): 656–62. doi:10.1086/342259. PMC 379202Freely accessible. PMID 12080485. 
  6. ^ a b "Entrez Gene: TREM2 triggering receptor expressed on myeloid cells 2". 
  7. ^ Guerreiro RJ, Lohmann E, Brás JM, Gibbs JR, Rohrer JD, Gurunlian N, Dursun B, Bilgic B, Hanagasi H, Gurvit H, Emre M, Singleton A, Hardy J (January 2013). "Using exome sequencing to reveal mutations in TREM2 presenting as a frontotemporal dementia-like syndrome without bone involvement". JAMA Neurol. 70 (1): 78–84. doi:10.1001/jamaneurol.2013.579. PMID 23318515. 
  8. ^ Hickman SE, El Khoury J (2014). "TREM2 and the neuroimmunology of Alzheimer's disease". Biochem. Pharmacol. 88 (4): 495–8. doi:10.1016/j.bcp.2013.11.021. PMID 24355566. 
  9. ^ Kolata G (14 November 2012). "Alzheimer's Tied to Mutation Harming Immune Response". New York Times. Retrieved 15 November 2012. 
  10. ^ Lue LF, Schmitz C, Walker DG (2014). "What happens to microglial TREM2 in Alzheimer's disease: Immunoregulatory turned into immunopathogenic?". Neuroscience. doi:10.1016/j.neuroscience.2014.09.050. PMID 25281879. 
  11. ^ Piccio L, Buonsanti C, Cella M, Tassi I, Schmidt RE, Fenoglio C, Rinker J, Naismith RT, Panina-Bordignon P, Passini N, Galimberti D, Scarpini E, Colonna M, Cross AH (2008). "Identification of soluble TREM-2 in the cerebrospinal fluid and its association with multiple sclerosis and CNS inflammation". Brain. 131 (Pt 11): 3081–91. doi:10.1093/brain/awn217. PMC 2577803Freely accessible. PMID 18790823. 

Further reading[edit]

External links[edit]