TREM2

2018-01-17T17:16:36Z

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{{Infobox_gene}}
'''Triggering receptor expressed on myeloid cells 2''' also known as '''TREM-2''' is a [[protein]] that in humans is encoded by the ''TREM2'' [[gene]].<ref name="pmid10799849">{{cite journal | vauthors = Bouchon A, Dietrich J, Colonna M | title = Cutting edge: inflammatory responses can tgih triggered by TREM-1, a novel receptor expressed on neutrophils and monocytes | journal = J. Immunol. | volume = 164 | issue = 10 | pages = 4991–5 | date = Jun 2000 | pmid = 10799849 | pmc = | doi = 10.4049/jimmunol.164.10.4991 }}</ref><ref name="pmid12080485">{{cite journal | vauthors = 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 | title = Mutations in two genes encoding different subunits of a receptor signaling complex result in an identical disease phenotype | journal = Am. J. Hum. Genet. | volume = 71 | issue = 3 | pages = 656–62 | date = Aug 2002 | pmid = 12080485 | pmc = 379202 | doi = 10.1086/342259 }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: TREM2 triggering receptor expressed on myeloid cells 2| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=54209| accessdate = }}</ref>

== Function ==

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 receptor]]s, [[CD14]] and [[Toll-like receptor]]s (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 superfamily|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]]).<ref name="entrez"/>

== Clinical significance ==

[[Homozygous]] mutations in TREM2 are known to cause rare, [[autosomal recessive]] forms of [[dementia]] with an early onset and presenting with<ref name="pmid12080485"/> or without<ref name="pmid23318515">{{cite journal | vauthors = 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 | title = Using exome sequencing to reveal mutations in TREM2 presenting as a frontotemporal dementia-like syndrome without bone involvement | journal = JAMA Neurol. | volume = 70 | issue = 1 | pages = 78–84 | date = January 2013 | pmid = 23318515 | doi = 10.1001/jamaneurol.2013.579 | pmc=4001789}}</ref> 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.<ref name="pmid24355566">{{cite journal | vauthors = Hickman SE, El Khoury J | title = TREM2 and the neuroimmunology of Alzheimer's disease | journal = Biochem. Pharmacol. | volume = 88 | issue = 4 | pages = 495–8 | year = 2014 | pmid = 24355566 | doi = 10.1016/j.bcp.2013.11.021 | pmc=3972304}}</ref><ref>{{cite news | author = Kolata G | title = Alzheimer’s Tied to Mutation Harming Immune Response | url = https://www.nytimes.com/2012/11/15/health/gene-mutation-that-hobbles-immune-response-is-linked-to-alzheimers.html?_r=0 | accessdate = 15 November 2012 | newspaper = New York Times | date = 14 November 2012}}</ref> TREM2 mutations increase the risk of neurodegenerative conditions such as Alzheimer's disease, [[amyotrophic lateral sclerosis]], and [[Parkinson's disease]]. TREM2 interacts with [[TYROBP|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.<ref name="pmid25281879">{{cite journal | vauthors = Lue LF, Schmitz C, Walker DG | title = What happens to microglial TREM2 in Alzheimer's disease: Immunoregulatory turned into immunopathogenic? | journal = Neuroscience | volume = 302| issue = | year = 2014 | pmid = 25281879 | doi = 10.1016/j.neuroscience.2014.09.050 | pages=138–50}}</ref>

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.<ref name="pmid18790823">{{cite journal | vauthors = 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 | title = Identification of soluble TREM-2 in the cerebrospinal fluid and its association with multiple sclerosis and CNS inflammation | journal = Brain | volume = 131 | issue = Pt 11 | pages = 3081–91 | year = 2008 | pmid = 18790823 | pmc = 2577803 | doi = 10.1093/brain/awn217 }}</ref>
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== References ==
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== Further reading ==
{{Refbegin|35em}}
* {{cite journal | vauthors = Del Bono N, Dente FL, Del Bono L | title = Identification of a novel soluble TREM-2 protein in the cerebrospinal fluid in association with central nervous system inflammation. | journal = Brain |year= 2008 | volume = 131 | pages = 3081–3091 | pmc = 2577803 | pmid=18790823 | doi=10.1093/brain/awn217}}
* {{cite journal | vauthors = Allcock RJ, Barrow AD, Forbes S, Beck S, Trowsdale J | title = The human TREM gene cluster at 6p21.1 encodes both activating and inhibitory single IgV domain receptors and includes NKp44 | journal = Eur. J. Immunol. | volume = 33 | issue = 2 | pages = 567–77 | year = 2003 | pmid = 12645956 | doi = 10.1002/immu.200310033 }}
* {{cite journal | vauthors = Soragna D, Papi L, Ratti MT, Sestini R, Tupler R, Montalbetti L | title = An Italian family affected by Nasu-Hakola disease with a novel genetic mutation in the TREM2 gene | journal = J. Neurol. Neurosurg. Psychiatry | volume = 74 | issue = 6 | pages = 825–6 | year = 2003 | pmid = 12754369 | pmc = 1738498 | doi = 10.1136/jnnp.74.6.825-a }}
* {{cite journal | vauthors = Cella M, Buonsanti C, Strader C, Kondo T, Salmaggi A, Colonna M | title = Impaired differentiation of osteoclasts in TREM-2-deficient individuals | journal = J. Exp. Med. | volume = 198 | issue = 4 | pages = 645–51 | year = 2003 | pmid = 12913093 | pmc = 2194167 | doi = 10.1084/jem.20022220 }}
* {{cite journal | vauthors = Paloneva J, Mandelin J, Kiialainen A, Bohling T, Prudlo J, Hakola P, Haltia M, Konttinen YT, Peltonen L | title = DAP12/TREM2 deficiency results in impaired osteoclast differentiation and osteoporotic features | journal = J. Exp. Med. | volume = 198 | issue = 4 | pages = 669–75 | year = 2003 | pmid = 12925681 | pmc = 2194176 | doi = 10.1084/jem.20030027 }}
* {{cite journal | vauthors = Montalbetti L, Ratti MT, Greco B, Aprile C, Moglia A, Soragna D | title = Neuropsychological tests and functional nuclear neuroimaging provide evidence of subclinical impairment in Nasu-Hakola disease heterozygotes | journal = Funct. Neurol. | volume = 20 | issue = 2 | pages = 71–5 | year = 2005 | pmid = 15966270 | doi = }}
* {{cite journal | vauthors = Bianchin MM, Lima JE, Natel J, Sakamoto AC | title = The genetic causes of basal ganglia calcification, dementia, and bone cysts: DAP12 and TREM2 | journal = Neurology | volume = 66 | issue = 4 | pages = 615–6; author reply 615–6 | year = 2006 | pmid = 16505336 | doi = 10.1212/01.wnl.0000216105.11788.0f }}
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== External links ==
* [https://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=plosl GeneReviews/NIH/NCBI/UW entry on Polycystic Lipomembranous Osteodysplasia with Sclerosing Leukoencephalopathy (PLOSL)]

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TREM2