Neurogenic locus notch homolog protein 3 (Notch 3) is a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
that in humans is encoded by the ''NOTCH3''
gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...
.
Function
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.
Pathology
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.
Adult Notch3 knock-out mice show incomplete neuronal maturation in the spinal cord dorsal horn, resulting in permanently increased nociceptive sensitivity.
Mutations in
NOTCH3
Neurogenic locus notch homolog protein 3 (Notch 3) is a protein that in humans is encoded by the ''NOTCH3'' gene.
Function
This gene encodes the third discovered human homologue of the ''Drosophila melanogaster'' type I membrane protein notch ...
are associated to
lateral meningocele syndrome
Lateral meningocele syndrome, also known as Lehman syndrome, is a very rare skeletal disorder with facial anomalies, hypotonia, and meningocele-related neurologic dysfunction. These protrusions form from membranes surrounding the spinal cord in gap ...
.
Pharmaceutical target
Notch3 is being investigated as a target for anti-cancer drugs, as it is overexpressed in several types of cancers. Early clinical trials of
Pfizer
Pfizer Inc. ( ) is an American multinational pharmaceutical and biotechnology corporation headquartered on 42nd Street in Manhattan, New York City. The company was established in 1849 in New York by two German entrepreneurs, Charles Pfizer ...
's PF-06650808, an anti-Notch3 antibody linked to a cytotoxic drug, showed efficacy against solid tumors.
References
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External links
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{{Notch signaling pathway