Oxidative Stress and β-Amyloid Protein in Alzheimer's Disease

Oxidative stress has been proposed to be an important factor in the pathogenesis of Alzheimer's disease (AD) and contributed to beta-amyloid (A beta) generation. Interaction between oxidative stress and neuro-inflammation leads to A beta generation. AD is associated with an increase in blood-brain barrier (BBB) permeability due to tight junction involvement. Oxidative stress decreases the expression of low-density lipoprotein receptor-related protein 1 and up-regulates receptor for advanced glycation end products in BBB and increases the BBB permeability, which could potentially lead to increased deposition of A beta within AD brain. Apoptosis takes place in the pathogenesis of AD, and oxidative stress contributes to apoptosis through both extrinsic pathway and intrinsic pathway. Oxidative stress-induced apoptosis may be a potential factor to A beta generation. A beta generation requires two sequential cleavages of APP, with the two proteolytic enzymes: beta-secretase and gamma-secretase. Oxidative damage up-regulates Ab via inducing activity of beta- and gamma-secretases. In this review, we will focus on the mechanism and pathway that oxidative stress contributes to A beta generation.