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Peptide (C)RDSHLGPHRSTPESR, corresponding to amino acid residues 345-359 of rat Psen1 (Accession P97887). 3rd cytoplasmic loop (at the Psen1 CTF subunit).
Immuno-colocalization of Calnexin and Presenilin-1 in mouse cortexImmunohistochemical staining of perfusion-fixed frozen mouse parietal cortex sections using Anti-Presenilin-1-ATTO-488 Antibody (#AIP-011-AG), (1:60) and Anti-Calnexin-ATTO-594 Antibody (#ACS-009-AR), (1:60). A. Calnexin staining (red) appears in neuronal profiles. B. Presenilin-1 staining (green) in the same section appears in neuronal profiles and apical dendrites (arrows). C. Merger of A and B demonstrates colocalization in several neurons (arrows). Cell nuclei are stained using DAPI (blue) as the counterstain. Images were acquired with 25x objective.Immuno-colocalization of Calnexin and Presenilin-1 in mouse hippocampusImmunohistochemical staining of perfusion-fixed frozen mouse hippocampal sections using Anti-Presenilin-1-ATTO-488 Antibody (#AIP-011-AG), (1:60) and Anti-Calnexin-ATTO-594 Antibody (#ACS-009-AR), (1:60). A. Calnexin staining (red) appears in neuronal profiles. B. Presenilin-1 staining (green) in the same section appears in neuronal profiles and apical dendrites (arrows). C. Merger of A and B demonstrates colocalization in several neurons (arrows). Cell nuclei are stained using DAPI (blue) as the counterstain. Images were acquired with 25x objective.
Presenilin-1 (PSEN1) is a transmembrane protein encoded by the PS1 gene. The protein is comprised of 9 transmembrane domains. The N- and C-termini of the protein are cytosolic and lumenal respectively. PSEN1, together with three other proteins- nicastrin, presenilin enhancer 2 and anterior pharynx-defective 1 form a protein complex named γ-Secretase. PSEN1 serves as the catalytic subunit of the γ-secretase complex. This complex, along with α- and β-secretases cleaves the amyloid precursor protein (APP). APP is the precursor for β-Amyloid fibrils which are the pathological hallmark of Alzheimer's disease (AD) and mutations in the PSEN1 gene have been implicated in AD pathophysiology. Currently, it remains unclear whether PSEN1 mutations cause disease by a loss of function or a gain of toxic function mechanism1.
PS1 mutations causing an overexpression of mutant human PSEN1 also increase the expression of ryanodine receptor 3 in PC12 cells. In addition, PC12 and cortical neuron cells expressing mutant PSEN1 exhibit increased calcium responses to caffeine compared with cells expressing wildtype PSEN1. This enhanced release of calcium is associated with increased cell vulnerability to β-Amyloid and caffeine induced cellular death. It has been hypothesized that PSEN1 and RyR interact directly2.
PS1 mutations also enhance inositol triphosphate (IP3)-mediated Ca2+ release in non-excitable and excitable cells. IP3-evoked Ca2+ responses are more than threefold greater in PS1M146V knock-in mice relative to non-transgenic controls. These mutations specifically disrupt intracellular Ca2+ release rather than reduce cytosolic Ca2+ buffering or clearance3.
Species reactivity key:
Anti-Presenilin-1 Antibody (#AIP-011) is a highly specific antibody directed against an epitope of the rat protein. The antibody can be used in western blot and immunohistochemistry applications. It has been designed to recognize PSEN1 from rat, mouse, and human samples.
Anti-Presenilin-1-ATTO-488 Antibody (#AIP-011-AG) is directly labeled with ATTO-488 fluorescent dye. ATTO dyes are characterized by strong absorption (high extinction coefficient), high fluorescence quantum yield, and high photo-stability. The ATTO-488 label is analogous to fluorescein isothiocyanate (FITC) and can be used with filters typically used to detect FITC. Anti-Presenilin-1-ATTO-488 Antibody has been tested in immunohistochemistry applications and is specially suited to experiments requiring simultaneous labeling of different markers.
- Anti-Calnexin Antibody (#ACS-009)
- Anti-Ryanodine Receptor 1 Antibody (#ARR-001)
- Anti-Ryanodine Receptor 2 Antibody (#ARR-002)
- Anti-Ryanodine Receptor 3 Antibody (#ARR-003)
- Anti-IP3 Receptor-1 (ITPR1) Antibody (#ACC-019)
- Anti-IP3 Receptor-2 (ITPR2) Antibody (#ACC-116)
- Anti-IP3 Receptor-2 (ITPR2)-ATTO-594 Antibody (#ACC-116-AR)