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 residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...
that in humans is encoded by the ''NOTCH3''
gene
In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
.
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
CADASIL or CADASIL syndrome, involving cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, is the most common form of hereditary stroke disorder and is thought to be caused by mutations of the '' NOTCH3'' gen ...
).
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 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 corporation, multinational Pharmaceutical industry, pharmaceutical and biotechnology corporation headquartered at The Spiral (New York City), The Spiral in Manhattan, New York City. Founded in 184 ...
's PF-06650808, an anti-Notch3 antibody linked to a cytotoxic drug, showed efficacy against solid tumors.
References
Further reading
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External links
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{{Notch signaling pathway