Effects of Hypoxia and Oxidative Stress on Expression of Neprilysin in Human Neuroblastoma Cells and Rat Cortical Neurones and Astrocytes |
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Authors: | Lilia Fisk Natalia N. Nalivaeva John P. Boyle Christopher S. Peers Anthony J. Turner |
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Affiliation: | (1) Institute of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Mount Preston Street, Leeds, LS2 9JT, UK;(2) AU Cardiovascular Medicine, University of Leeds, Leeds, LS2 9JT, UK |
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Abstract: | Pathogenesis of Alzheimer’s disease (AD), which is characterised by accumulation of extracellular deposits of β-amyloid peptide (Aβ) in the brain, has recently been linked to vascular disorders such as ischemia and stroke. Aβ is constantly produced in the brain from amyloid precursor protein (APP) through its cleavage by β- and γ-secretases and certain Aβ species are toxic for neurones. The brain has an endogenous mechanism of Aβ removal via proteolytic degradation and the zinc metalloproteinase neprilysin (NEP) is a critical regulator of Aβ concentration. Down-regulation of NEP could predispose to AD. By comparing the effects of hypoxia and oxidative stress on expression and activity of the Aβ-degrading enzyme NEP in human neuroblastoma NB7 cells and rat primary cortical neurones we have demonstrated that hypoxia reduced NEP expression at the protein and mRNA levels as well as its activity. On contrary in astrocytes hypoxia increased NEP mRNA expression. Special issue dedicated to Dr. Moussa Youdim. |
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Keywords: | Human neuroblastoma NB7 cells Aβ -degrading enzymes Neprilysin Hypoxia Oxidative stress Primary cortical neurones Astrocytes Alzheimer’ s disease |
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