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Nct is required for neuronal survival during aging and normal lifespan.
Down-regulation of the ATP-binding cassette transporter 2 (Abca2 (show ABCA2 Proteins)) reduces amyloid-beta production by altering Nicastrin maturation and intracellular localization.
Co-expression of Drosophila Pen-2 (show PSENEN Proteins) with Aph-1 and nicastrin increases the formation of Psn fragments as well as gamma-secretase activity
Aph-1 and Nct may form a subcomplex that stabilizes the Psn holoprotein at an early step in gamma-secretase assembly.
the proper assembly of the Aph-1.nicastrin subcomplex with presenilin is the prerequisite for the trafficking as well as the enzymatic activity of the gamma-secretase complex and Aph-1 functions as a stabilizing scaffold in the assembly of this complex
presenilin, nicastrin, APH-1, and PEN-2 (show PSENEN Proteins), are present and enriched on phagosome membranes from both murine macrophages and Drosophila S2 phagocytes
Nicastrin is essential to early photoreceptor neuron development
Zebrafish have an orthologue of human NCSTN, transcripts of the zebrafish ncstn gene are provided maternally, and the gene is then transcribed throughout embryogenesis and in adult zebrafish. Zebrafish ncstn transcripts are present in ventricular cells of the developing brain, Ncstn protein likely plays a role in Notch (show NOTCH1 Proteins) signaling within the proliferative ventricular zone.
The results show no differences in the decreased levels of inflammatory factors between patients with and without NCSTN mutations. This result may indicate that NCSTN mutations have no direct effect on inflammatory cells in the process of cytokine production.
The authors identified two nonsynonymous mutations in NCSTN in a white population, one of which had previously been described in African American and Chinese patients with HS. In addition, several intronic polymorphisms within the NCSTN were identified that were present at a significantly higher frequency in the HS population.
The results lead the investigators to speculate that NCSTN may be one of the genes determining the clinical phenotype of follicular HS .
Loss of function of nicastrin impacts on cell proliferation and differentiation-associated signalling pathways in a keratinocyte cell line.
analysis of two novel mutations segregating with familial hidradenitis suppurativa (acne inversa) and acne conglobate in NCSTN
Case Report: large Chinese family harboring novel NCSTN mutation associated with acne inversa.
Nicastrin mutation is associated with schizophrenia.
haploinsufficiency of the NCSTN gene caused by the nonsense mutation c.1258C>T (p.Q420X) contributes to the occurrence of hidradenitis suppurativa in this family.
The "Lid" domain of nicastrin is not essential for regulating gamma-secretase activity.
SNPs in Notch (show NOTCH1 Proteins) pathway genes may be predictors of cutaneous melanoma disease-specific survival.
mice defective of the nicastrin subunit of gamma-secretase in oligodendrocytes have hypomyelination in the central nervous system.
The results of this study showed that elevated p-tau levels in NCT cKO mice and have demonstrated that changes on p-tau were likely caused by enhanced activity of CDK5 but not GSK3beta.
PS1 (show PSEN1 Proteins)(exon8) interacts with nicastrin, participating in the gamma-secretase complex formation.
nicastrin plays essential roles in the regulation of short- and long-term synaptic plasticity, highlighting the importance of gamma-secretase in the function of mature synapses
These results reveal a key role for ncstn in modulating amyloid beta production and amyloid plaque formation.
Upregulation of PS1 (show PSEN1 Proteins)/gamma-secretase activity may be a risk factor for late onset sporadic Alzheimer's disease.
Pen-2, as well as nicastrin and Aph-1alpha, is dispensable for presenilin endoproteolysis
SGK1 (show SGK1 Proteins) is a gamma-secretase regulator presumably effective through phosphorylation and degradation of NCT.
We propose a model that identifies critical TMDs of Aph-1 for associations with Nct and PS for the stepwise assembly of gamma-secretase components.
This gene encodes a Type I transmembrane glycoprotein that is an integral component of the multimeric gamma-secretase complex. The encoded protein cleaves integral membrane proteins, including Notch receptors and beta-amyloid precursor protein, and may be a stabilizing cofactor required for gamma-secretase complex assembly. The cleavage of beta-amyloid precursor protein yields amyloid beta peptide, the main component of the neuritic plaque and the hallmark lesion in the brains of patients with Alzheimer's disease\; however, the nature of the encoded protein's role in Alzheimer's disease is not known for certain. Alternatively spliced transcript variants have been described, but their full-length nature has not been determined.
, anterior pharynx-defective 2
, membrane protein