NOTCH3

This gene encodes the third discovered human homologue of the Drosophila melanogaster type I membrane protein notch. In Drosophila, notch interaction with its cell-bound ligands (delta, serrate) establishes an intercellular signalling pathway that plays a key role in neural development. Homologues of the notch-ligands have also been identified in human, but precise interactions between these ligands and the human notch homologues remains to be determined.

Image:CADASIL - very high mag.jpg showing CADASIL with a Notch 3 immunostain]]

Mutations in NOTCH3 have been identified as the underlying cause of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Mutations in NOTCH3 have also been identified in families with Alzheimer's disease.{{cite journal | vauthors = Guerreiro RJ, Lohmann E, Kinsella E, Brás JM, Luu N, Gurunlian N, Dursun B, Bilgic B, Santana I, Hanagasi H, Gurvit H, Gibbs JR, Oliveira C, Emre M, Singleton A | title = Exome sequencing reveals an unexpected genetic cause of disease: NOTCH3 mutation in a Turkish family with Alzheimer's disease | journal = Neurobiol. Aging | volume = 33 | issue = 5 | pages = 1008.e17–23 | year = 2012 | pmid = 22153900 | pmc = 3306507 | doi = 10.1016/j.neurobiolaging.2011.10.009 }} Adult Notch3 knock-out mice show incomplete neuronal maturation in the spinal cord dorsal horn, resulting in permanently increased nociceptive sensitivity.{{cite journal | vauthors = Rusanescu G, Mao J | title = Notch3 is necessary for neuronal differentiation and maturation in the adult spinal cord | journal = J. Cell. Mol. Med. | volume = 18 | issue = 10 | pages = 2103–16 | year = 2014 | pmid = 25164209 | pmc = 4244024 | doi = 10.1111/jcmm.12362 }}

Mutations in NOTCH3 are associated to lateral meningocele syndrome.{{cite journal | vauthors = Gripp KW, Robbins KM, Sobreira NL, Witmer PD, Bird LM, Avela K, Makitie O, Alves D, Hogue JS, Zackai EH, Doheny KF, Stabley DL, Sol-Church K | title = Truncating mutations in the last exon of NOTCH3 cause lateral meningocele syndrome | journal = Am. J. Med. Genet. A | year = 2014 | pmid = 25394726 | doi = 10.1002/ajmg.a.36863 | volume=167A | issue = 2 | pages=271–81| pmc = 5589071 }}

Notch3 is being investigated as a target for anti-cancer drugs, as it is overexpressed in several types of cancers.{{cite book |pmc=3361718|year=2012|last1=Purow|first1=B|title=Notch Signaling in Embryology and Cancer|volume=727|pages=305–319|doi=10.1007/978-1-4614-0899-4_23|chapter=Notch Inhibition as a Promising New Approach to Cancer Therapy|series=Advances in Experimental Medicine and Biology|isbn=978-1-4614-0898-7|pmid=22399357}} Early clinical trials of Pfizer's PF-06650808, an anti-Notch3 antibody linked to a cytotoxic drug, showed efficacy against solid tumors.{{Cite web|url=http://adcreview.com/pfizer-adc-development-overview-2016/|title = Pfizer Oncology: ADC Development Overview (2016) » ADC Review}}

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• {{MeshName|NOTCH3+protein,+human}}

{{Notch signaling pathway}}