Anti-Human Nicastrin (CT)

PN:N164

This polyclonal antibody is formulated in phosphate buffered saline (PBS) pH 7.4 containing 0.02% sodium azide as a preservative.

This polyclonal antibody is stable for at least one week when stored at 2-8°C. For long term storage, aliquot in working volumes without diluting and store at –20°C in a manual defrost freezer. Avoid Repeated Freeze Thaw Cycles.

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Rabbit Anti-Human Nicastrin recognizes an epitope near the C-terminus of Human, Mouse and Rat Nicastrin. This polyclonal antibody was purified using affinity chromatography.

Nicastrin, in addition to presenilin, PEN2, and APH-1 forms the γ-secretase protein complex, a membrane-bound aspartyl protease that can cleave certain proteins at peptide bonds buried within the hydrophobic environment of the lipid bilayer. This cleavage is responsible for a key step in signaling from several cell-surface receptors and is thought to be required for the generation of the neurotoxic amyloid peptides that are central to the pathogenesis of Alzheimer’s disease(1,2 for review). Like the tumor necrosis factor-a-converting enzyme (TACE) and the b-site cleavage enzyme (BACE) protease families, γ-secretase will cleave the amyloid precursor protein (APP), but within the intramembrane region of APP, resulting in either the non-toxic p3 (from the α and γ cleavage site) or the toxic Aβ amyloid peptide (from the β and γ cleavage site)(3). It is thought that accumulation of the Aβ peptide is the precursor to Alzheimer’s disease(4). Nicastrin is also thought to be involved in cell proliferation and signaling, especially in regards to activation of Notch receptors as loss of Nicastrin expression results in mouse embryonic lethality(5).

1. Weihofen A and Martoglio B. Intramembrane-cleaving proteases: controlled liberation of proteins and bioactive peptides. Trends Cell Biol. 2003; 13:71-8. 2. Periz G and Fortini ME. Functional reconstitution of γ-secretase through coordinated expression of presenilin, Nicastrin, aph-1, and pen-2. J. Neurosci. Res. 2004; 77:309-22. 3. Selkoe DJ. The cell biology of β-amyloid precursor protein and presenilin in Alzheimer’s disease. Trends Cell Biol. 1998; 8:447-53. 4. Selkoe SJ. Translating cell biology into therapeutic advances in Alzheimer’s disease. Nature 1999; 399:A23-31. 5. Nguyen V, Hawkins C, Bergeron C, et al. Loss of nicastrin elicits an apoptotic phenotype in mouse embryos. Brain Res. 2006; 1086:76-84.