Simultaneous activation of Nrf2 and elevation of antioxidant compounds for reducing oxidative stress and chronic inflammation in human Alzheimer's disease

Despite extensive research, neither the incidence nor the rate of progression of Alzheimer's disease (AD) has significantly changed. Some biochemical and genetic defects that initiate and promote AD include: (a) increased oxidative stress, (b) chronic inflammation (c) mitochondrial dysfunction, (d) A beta 1-42 peptides generated from the amyloid precursor protein (APP), (e) proteasome inhibition, and (f) mutations in APP, presenilin-1 and presenilin-2 genes. Increased oxidative stress appears to precede other biochemical and genetic defects. Oxidative damage induces chronic inflammation. Therefore, reducing these defects simultaneously may reduce the development and progression of AD. Previous studies with individual antioxidants produced consistent benefits in animal models of AD; however, a similar approach produced inconsistent results in human AD. This review proposes a hypothesis that simultaneous elevation of the levels of antioxidant enzymes and antioxidant compounds is necessary for optimally reducing oxidative stress and chronic inflammation in human AD. Supplementation can enhance the levels of antioxidant compounds; but elevation of antioxidant enzymes requires activation of Nrf2. This review discusses activation and regulation of Nrf2. The need for multi-antioxidants that can affect multi-targets has been proposed without specific recommendations. This review proposes a micronutrient mixture that would simultaneously enhance the levels of antioxidant enzymes and antioxidant compounds in human AD. (C) 2016 Elsevier Ireland Ltd. All rights reserved.