The NCSTN gene encodes nicastrin, an essential component of gamma secretase complexes. Gamma-secretases (γ-secretases) are transmembrane multiprotein complexes comprised of presenilin (PSEN1 or PSEN2), nicastrin (NCSTN), PSENEN (a.k.a. PEN2), and APH1 (APH1A or APH1B); gamma-secretases are responsible for intramembrane proteolytic cleavage of amyloid precursor protein (APP) and NOTCH receptor proteins. Both PSEN1 and PSEN2 are implicated in early-onset forms of Alzheimer disease (see human disease model reports for 'Alzheimer disease 3', FBhh0000120 and 'Alzheimer disease 4', FBhh0000121). In Drosophila, there is a single gene orthologous to human NCSTN, Dmel\Nct, for which classical loss-of-function alleles, RNAi-targeting constructs, and an allele caused by insertional mutagenesis have been generated.
The human NCSTN gene has not been introduced into flies.
Animals homozygous for loss-of-function mutations of Dmel\Nct typically die during the larval or pupal stage. Somatic clones in the wing exhibit Notch-like phenotypes. RNAi-effected knockdown of Nct in selected neurons of the adult brain results in shortened lifespan, climbing defects, increases in apoptosis, and age-dependent neurodegeneration; similar phenotypes are observed for RNAi-effected knockdown of Psn in comparable experiments (see human disease model report for 'Alzheimer disease, presenilin-related', FBhh0000623). Physical and genetic interaction(s) of Dmel\Nct have been described; see below and in the gene report for Nct.
[updated Jul. 2018 by FlyBase; FBrf0222196]
Alzheimer disease (AD) is the most common form of progressive dementia in the elderly. [from MIM:104300; 2016.01.08]
Memory loss is the most common sign of Alzheimer disease. As the disorder progresses, some people with AD experience personality and behavioral changes; other common symptoms include agitation, restlessness, withdrawal, and loss of language skills. Total care is usually required during the advanced stages of the disease. Affected individuals usually survive 8 to 10 years after the appearance of symptoms, but the course of the disease can range from 1 to 25 years. Death usually results from pneumonia, malnutrition, or general body wasting. [from Genetics Home Reference, Alzheimer disease; 2016.01.08]
Alzheimer disease can be classified as early-onset or late-onset. The signs and symptoms of the early-onset form appear before age 65, while the late-onset form appears after age 65. The early-onset form is much less common than the late-onset form, accounting for less than 5 percent of all cases of Alzheimer disease. [from Genetics Home Reference, Alzheimer disease; 2016.01.08]
NCSTN encodes the transmembrane glycoprotein nicastrin, an essential subunit of the multimeric gamma-secretase complex; the gamma-secretase complex catalyzes the intramembrane cleavage of integral membrane proteins such as Notch receptors and APP (amyloid-beta precursor protein). [Gene Cards, NCSTN; 2018.07.09]
Nicastrin is a transmembrane glycoprotein that forms gamma-secretase complexes with presenilin-1 and presenilin-2. [from MIM:605254; 2018.07.09]
Gamma-secretase is a transmembrane multiprotein complex comprised of presenilin (PSEN1 or PSEN2), nicastrin (NCSTN), PSENEN, and APH1 (APH1A or APH1B); it is responsible for intramembrane proteolytic cleavage of amyloid precursor protein (APP) and NOTCH receptor proteins. [from MIM:104311; 2018.07.09]
One to one: 1 human to 1 Drosophila.
High-scoring ortholog of human NCSTN (1 Drosophila to 1 human). Dmel\Nct shares 31% identity and 49% similarity with the human gene.
