NRF2 and NF-қB interplay in Cerebrovascular and Neurodegenerative disorders: Molecular Mechanisms and Possible Therapeutic Approaches

Publication date: Available online 28 November 2018Source: Redox BiologyAuthor(s): Farzane Sivandzade, Shikha Prasad, Aditya Bhalerao, Luca CuculloAbstractElectrophiles and reactive oxygen species (ROS) play a major role in modulating cellular defense mechanisms as well as physiological functions, and intracellular signaling. However, excessive ROS generation (endogenous and exogenous) can create a state of redox imbalance leading to cellular and tissue damage 1. A growing body of research data strongly suggests that imbalanced ROS and electrophile overproduction are among the major prodromal factors in the onset and progression of several cerebrovascular and neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS), stroke, Alzheimer's disease (AD), Parkinson's disease (PD), and aging 1–6. Cells offset oxidative stress by the action of housekeeping antioxidative enzymes (such as superoxide dismutase, catalase, glutathione peroxidase) as well direct and indirect antioxidants 7. The DNA sequence responsible for modulating the antioxidative and cytoprotective responses of the cells has been identified as the antioxidant response element (ARE), while the nuclear factor erythroid 2-related factor (NRF2) is the major regulator of the xenobiotic-activated receptor (XAR) responsible for activating the ARE-pathway, thus defined as the NRF2-ARE system1. In addition, the interplay between the NRF2-ARE system and nuclear factor kappa-light-chain-enhancer of activated B c...
Source: Redox Biology - Category: Biology Source Type: research