Impacts of oxidants and antioxidants on the emergence and progression of Alzheimer's disease

The brain shows a high sensitivity to oxidative stress (OS). Thus, the maintenance and homeostasis of the brain, in particular neural cells, regarding the reduction-oxidation (redox) situation is crucial for the regular function of the central nervous systems (CNS). The imbalance between the reactive oxygen species (ROS) and the cellular mechanism(s) might lead to the emergence of OS, resulting in possible cell death and tissue damages, and initiating neurodegenerative disorders (NDDs). Characterized by the cytoplasmic growth of neurofibrillary tangles and extracellular β-amyloid plaques, Alzheimer's disease (AD) is a complex NDD that causes dementia in adult life with severe manifestations. Nuclear factor erythroid 2-related factor 2 (NRF2) is a key transcription factor that regulates the functional expression of OS-related genes and the functionality of endogenous antioxidants in response to ROS. In the case of oxidative damage, NRF2 is transferred to the nucleus and attached to the antioxidant response element (ARE), which can subsequently enhance the functional expression of the cell-protecting genes. In this review, we impart on the key mechanisms engaged in the generation of active and reactive species of endogenous and exogenous oxidants and discuss the antioxidants as the defense system of neural cells regarding the NRF2-ARE signaling path in the CNS.