CD10 / Neprilysin antibody

Background of CD10 / Neprilysin antibody

The mammalian neprilysin (NEP) family members are typically type II membrane endopeptidases responsible for the activation/inactivation of neuropeptides and peptide hormones. The substrate specificity and subcellualar localization of the 7 mammalian NEPs contribute to their functional heterogeneity. Proteolytic enzymes constitute around 2% of the human genome and are several stages of cell development from fertilization to cell death as a result of apoptosis. The identification of many novel proteases from genome-sequencing programs has suggested them as potential new therapeutic targets. In addition, several well-characterized metallopeptidases were recently shown to possess new biological roles in neuroinflammation and neurodegeneration. Neprilysin, a zinc-metalloendopeptidase, located on chromosome 3q21-q27 contains 24 exons and plays important role in the physiology and pathology of many diseases such as hypertension, cancer and Alzheimer’s disease (AD). In AD the deposition of amyloid beta peptides (Abeta) in brain form plaques that are hallmark of AD codition. Neprilysin is the major Abeta degrading enzyme and a reduction in Neprilysin activity contribute to the extent of plaque formation in AD by increasing the steady state levels of Abeta (1). The levels of Abeta in the central nervous system are regulated by several catabolic proteases, including insulysin (IDE), BACE1, BACE2, presenilin1, presenilin2, gamma secretase and neprilysin (NEP). Gleevec, a known tyrosine kinase inhibitor, has been shown to lower Abeta secretion, and it is considered a potential basis for novel therapies for Alzheimer’s disease. In vitro treatment of cells with Gleevec elevates neprilysin levels that caused an increased Abeta degradation (2).
Neutral endopeptiddase, Neprilysin is a major enzyme involved in the degradation and metablic inactivation of a number of biological peptides including enkephlins, substance P, bradykinin, incretin hormone glucagon like peptide 1 and arterial natriuretic peptides. Neprilysin hydrolyze the brain derived natriuretic peptide (BNP) but not the structurally related arterial or and C-type natriuretic peptides which are important cardioprotective hormones with essential function in sodium excretion, water balance, and blood pressure regulation. The Neprilysin is a 750 amino acid protein with predicted molecular weight of 86 kDa but as a result of abundant post translational modifications, specially glycosylation, the brain Neprilysin migrates between 98-110 kDa on denaturing SDS-PAGE. The Neprilysin is a membrane bound glycoprotein with a short N-termainl cytoplasmic tail, and TMD and a large C-terminal extracellular catalytic domain comprise of a zinc binding motif that also facilitates the small hydrophobic peptides. The Neprilysin is ubiquitously expressed in many tissues including intestinal BBM, kidney epithelial cells, neutrophils, thymocytes, lung, testis and in neuronal plasma brain (3).