Effects of hypoxia and oxidative stress on expression of neprilysin in human neuroblastoma cells and rat cortical neurones and astrocytes

Pathogenesis of Alzheimer's disease (AD), which is characterised by accumulation of extracellular deposits of beta-amyloid peptide (A beta) in the brain, has recently been linked to vascular disorders such as ischemia and stroke. A beta is constantly produced in the brain from amyloid precursor protein (APP) through its cleavage by beta- and gamma-secretases and certain A beta species are toxic for neurones. The brain has an endogenous mechanism of A beta removal via proteolytic degradation and the zinc metalloproteinase neprilysin (NEP) is a critical regulator of A beta concentration. Down-regulation of NEP could predispose to AD. By comparing the effects of hypoxia and oxidative stress on expression and activity of the A beta-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.