Anti-Presenilin-1-ATTO Fluor-488 Antibody

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.