- Peptide (C)RDSHLGPHRSTPESR, corresponding to amino acid residues 345-359 of rat Psen1 (Accession P97887). 3rd cytoplasmic loop (at the Psen1 CTF subunit).
- Western blot analysis of rat pancreas membrane (lanes 1 and 4), rat hippocampus (lanes 2 and 5) and mouse pancreatic cancer cell line (MS1) (lanes 3 and 6):1-3. Anti-Presenilin-1 Antibody (#AIP-011), (1:500).
4-6. Anti-Presenilin-1 Antibody, preincubated with Presenilin-1 Blocking Peptide (#BLP-IP011).
- Expression of Presenilin-1 in mouse brainImmunohistochemical staining of mouse hippocampus and mouse cerebellum using Anti-Presenilin-1 Antibody (#AIP-011), (1:600). A. In hippocampus, PS-1 staining (green) appears in apical dendrites of pyramidal neurons (arrows). B. In cerebellum, an intense staining for PS-1 (green) appears in dendritic trees of Purkinje cells (arrows). A moderate staining is detected in the granule layer and in the soma of Purkinje and molecular layer interneurons. In both panels DAPI is used as the counterstain.
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 Fluor-488 Antibody (#AIP-011-AG).
A fluorescent labeled primary antibody. It can be used in multiplex staining studies in conjunction with any of our antibodies raised in rabbit.