Psychiatry related information on Ncstn

• This result suggests that complete disruption of presenilin complexes elicits programmed cell death, in addition to a Notch phenotype, which may contribute to the developmental abnormalities and embryonic mortality of nicastrin-null mice and possibly neurodegeneration in Alzheimer's disease [1].

High impact information on Ncstn

• Presenilin interacts with nicastrin, APH-1 and PEN-2 (ref. 6), all of which are required for gamma-secretase function [2].
• Gamma-secretase depends on presence of presenilins (PS), Nct, Aph-1, and PEN-2 within a core complex [3].
• Interestingly, significant amounts of full-length PS1 and PEN-2, but not APH-1, are detected on the plasma membrane in Nct KO cells, suggesting the Nct-independent cell surface delivery of the PEN-2.PS1 [4].
• Presenilin 1 and presenilin 2 have differential effects on the stability and maturation of nicastrin in Mammalian brain [5].
• Post-translational glycosylation and trafficking of nicastrin is necessary for the activity of these complexes [5].

Biological context of Ncstn

• Alleles at the Nicastrin locus modify presenilin 1- deficiency phenotype [6].
• We report here that although there are differences in the post-translational processing of nicastrin in neurons and glia, both of the presenilins are required for the physiological post-translational modification and for the correct subcellular distribution of nicastrin [5].
• Finally, we show that NCT expression peaked 24 h after NCT cDNA transfection of wild-type and NCT-/- fibroblasts, while neprilysin expression drastically increased only after 36 h and was maximal at 48 h [7].
• Preceding their mortality, 10.5-day-old nicastrin-null embryos were found to also exhibit specific apoptosis within regions showing profound deformities, particularly in the developing heart and brain [1].
• APH-1 (anterior pharynx defective) along with nicastrin and PEN-2 (presenilin enhancer) are essential components of the presenilin (PS)-dependent gamma-secretase complex [8].

Anatomical context of Ncstn

• In adult mouse, nicastrin is highly expressed in muscle membranes, whereas presenilin levels are very low [9].
• We also show that endogenous PEN2 expression was drastically higher in wild-type than in PS- and Nct-deficient fibroblasts and was enhanced by proteasome inhibitors only in the two deficient cell systems [10].
• Nicastrin-null embryos died by embryonic day 10.5 and exhibited several patterning defects, including abnormal somite segmentation, phenotypes that are reminiscent of embryos lacking Notch1 or both presenilins [11].
• In N2a and 293 cell lines that stably overexpress PS1, APH-1, NCT, and PEN-2, PS1 fragment levels are elevated by up to 10-fold over endogenous levels [12].
• AVs were also the most enriched subcellular fraction in levels of the gamma-secretase components presenilin and nicastrin [13].

Associations of Ncstn with chemical compounds

• After RA treatment the NICA siRNA clone failed to differentiate completely into networks of neurons [14].

Physical interactions of Ncstn

• Together, these results establish that nicastrin is an essential component of the multimeric gamma-secretase complex in mammals required for both gamma-secretase activity and APP trafficking and suggest that nicastrin may be a valuable therapeutic target for Alzheimer's disease [11].

Other interactions of Ncstn

• Neprilysin activity and expression are controlled by nicastrin [7].

References