Neurogenic locus notch homolog protein 3(Notch 3) is a protein that in humans is encoded by the NOTCH3 gene. [5] [6]
Neurogenic locus notch homolog protein 3(Notch 3) is a protein that in humans is encoded by the NOTCH3 gene. [5] [6]
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.
Mutations in NOTCH3 have been identified as the underlying cause of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). [6] Mutations in NOTCH3 have also been identified in families with Alzheimer's disease. [7] Adult Notch3 knock-out mice show incomplete neuronal maturation in the spinal cord dorsal horn, resulting in permanently increased nociceptive sensitivity. [8] Mutations in NOTCH3 are associated to lateral meningocele syndrome. [9]
Notch3 is being investigated as a target for anti-cancer drugs, as it is overexpressed in several types of cancers. [10] Early clinical trials of Pfizer's PF-06650808, an anti-Notch3 antibody linked to a cytotoxic drug, showed efficacy against solid tumors. [11]
Cerebrovascular disease includes a variety of medical conditions that affect the blood vessels of the brain and the cerebral circulation. Arteries supplying oxygen and nutrients to the brain are often damaged or deformed in these disorders. The most common presentation of cerebrovascular disease is an ischemic stroke or mini-stroke and sometimes a hemorrhagic stroke. Hypertension is the most important contributing risk factor for stroke and cerebrovascular diseases as it can change the structure of blood vessels and result in atherosclerosis. Atherosclerosis narrows blood vessels in the brain, resulting in decreased cerebral perfusion. Other risk factors that contribute to stroke include smoking and diabetes. Narrowed cerebral arteries can lead to ischemic stroke, but continually elevated blood pressure can also cause tearing of vessels, leading to a hemorrhagic stroke.
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 Notch 3 gene on chromosome 19. The disease belongs to a family of disorders called the leukodystrophies. The most common clinical manifestations are migraine headaches and transient ischemic attacks or strokes, which usually occur between 40 and 50 years of age, although MRI is able to detect signs of the disease years prior to clinical manifestation of disease.
A perivascular space, also known as a Virchow–Robin space, is a fluid-filled space surrounding certain blood vessels in several organs, including the brain, potentially having an immunological function, but more broadly a dispersive role for neural and blood-derived messengers. The brain pia mater is reflected from the surface of the brain onto the surface of blood vessels in the subarachnoid space. In the brain, perivascular cuffs are regions of leukocyte aggregation in the perivascular spaces, usually found in patients with viral encephalitis.
Familial hemiplegic migraine (FHM) is an autosomal dominant type of hemiplegic migraine that typically includes weakness of half the body which can last for hours, days, or weeks. It can be accompanied by other symptoms, such as ataxia, coma, and paralysis. Migraine attacks may be provoked by minor head trauma. Some cases of minor head trauma in patients with hemiplegic migraine can develop into delayed cerebral edema, a life-threatening medical emergency. Clinical overlap occurs in some FHM patients with episodic ataxia type 2 and spinocerebellar ataxia type 6, benign familial infantile epilepsy, and alternating hemiplegia of childhood.
The acetolactate synthase (ALS) enzyme is a protein found in plants and micro-organisms. ALS catalyzes the first step in the synthesis of the branched-chain amino acids.
Neurogenic locus notch homolog protein 1(Notch 1) is a protein encoded in humans by the NOTCH1 gene. Notch 1 is a single-pass transmembrane receptor.
Frizzled-2(Fz-2) is a protein that in humans is encoded by the FZD2 gene.
Frizzled-4(Fz-4) is a protein that in humans is encoded by the FZD4 gene. Fz-4 has also been designated as CD344.
Delta-like protein 1 is a protein that in humans is encoded by the DLL1 gene.
Protein patched homolog 1 is a protein that is the member of the patched family and in humans is encoded by the PTCH1 gene.
Krev interaction trapped protein 1 or Cerebral cavernous malformations 1 protein is a protein that in humans is encoded by the KRIT1 gene. This gene contains 16 coding exons and is located on chromosome 7q21.2. Loss of function mutations in KRIT1 result in the onset of cerebral cavernous malformation. Cerebral cavernous malformations (CCMs) are vascular malformations in the brain and spinal cord made of dilated capillary vessels.
Membrane protein MLC1 is a protein that in humans is encoded by the MLC1 gene.
Crumbs homolog 1 is a protein that in humans is encoded by the CRB1 gene.
Achaete-scute homolog 1 is a protein that in humans is encoded by the ASCL1 gene. Because it was discovered subsequent to studies on its homolog in Drosophila, the Achaete-scute complex, it was originally named MASH-1 for mammalian achaete scute homolog-1.
Mastermind-like protein 1 is a protein that in humans is encoded by the MAML1 gene.
Delta-like 3 (Drosophila), also known as DLL3, is a protein which in humans is encoded by the DLL3 gene. Two transcript variants encoding distinct isoforms have been identified for this gene.
Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL) is disease of the arteries in the brain, which causes tissue loss in the subcortical region of the brain and the destruction of myelin in the CNS. CARASIL is characterized by symptoms such as gait disturbances, hair loss, low back pain, dementia, and stroke. CARASIL is a rare disease, having only been diagnosed in about 50 patients, of which ten have been genetically confirmed. Most cases have been reported in Japan, but Chinese and caucasian individuals have also been diagnosed with the disease. CARASIL is inherited in an autosomal recessive pattern. There is currently no cure for CARASIL. Other names for CARASIL include familial young-adult-onset arteriosclerotic leukoencephalopathy with alopecia and lumbago without arterial hypertension, Nemoto disease and Maeda syndrome.
Marie-Germaine Bousser is a French neuroscientist. She won the Brain Prize in 2019 for her work on CADASIL.
Élisabeth Tournier-Lasserve is a French neurologist, medical geneticist, university professor and hospital practitioner in genetics. Together with three colleagues, she was the co-recipient of the Brain Prize in 2019, the world's largest brain research prize.
Anne Joutel is a French neurologist and neuroscientist who is Research Director at the Institute of Psychiatry and Neurosciences of Paris. In 2019, together with three colleagues, she was awarded the Brain Prize, the largest prize awarded for brain research.