Journal de la maladie d'Alzheimer et du parkinsonisme

Abstrait

Simultaneous Activation of Nrf2, Elevation of Antioxidants and Reduction in Glutamate Level: An Essential Strategy for Prevention and Improved Management of Neurodegenerative Diseases

Kedar N Prasad

Despite extensive research on the biochemical and genetic defects in Alzhemier’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD) and post-traumatic stress disorders (PTSDs), there are no effective preventive strategies; and the treatment methods remain unsatisfactory. The reviews of these studies suggested that enhanced production of free radicals, persistence inflammation were one of the earliest events in the development and progression of these diseases. Excess release of glutamate occurred in HD and PTSD earlier than in AD and PD. Glutamate together with excess free radicals and pro-inflammatory cytokines participate in the progression of these diseases. Thus, reducing simultaneously these biochemical defects may prevent, and together with standard therapy, enhance the care of neurodegenerative diseases. Previous studies using primarily individual antioxidants produced variable outcomes ranging from transient benefits in the early phase of the disease to no effect. In order to optimally attenuate oxidative stress, persistence inflammation and glutamate, it is necessary to simultaneously increase the cellular levels of cytoprotective enzymes including antioxidant enzymes, antioxidant compounds that are derived from the diet and made in the body and reduce glutamate level. Enhancement of antioxidant compounds and attenuation of glutamate level are achieved by supplementation with antioxidants and B-vitamins; however, increasing the cellular levels of antioxidant enzymes needs an activation of Nr2 that is ROS-dependent and ROSindependent. In neurodegenerative diseases, Nrf2 is not activated by ROS; however, antioxidants activate ROSindependent Nrf2. This commentary briefly describes the genetic and epigenetic factors that regulate the activation of Nrf2, and proposes a micronutrient mixture that may simultaneously activate ROS-independent Nrf2, increase the cellular levels of antioxidants, and decrease the release and toxicity of glutamate. This micronutrient mixture may simultaneously and optimally reduce oxidative, chronic inflammation and glutamate, and thus, may prevent and together with standard therapy, enhance the care of these neurodegenerative diseases.