Reactive Oxygen Species, Redox Signaling and Neuroinflammation in Alzheimer's Disease: The NF-κB Connection

Abstract

Oxidative stress and inflammatory response are important elements of Alzheimer's disease (AD) pathogenesis, but the role of redox signaling cascade and its cross-talk with inflammatory mediators have not been elucidated in details in this disorder. The review summarizes the facts about redox-signaling cascade in the cells operating through an array of kinases, phosphatases and transcription factors and their downstream components. The biology of NF-κB and its activation by reactive oxygen species (ROS) and proinflammatory cytokines in the pathogenesis of AD have been specially highlighted citing evidence both from post-mortem studies in AD brain and experimental research in animal or cell-based models of AD. The possibility of identifying new disease-modifying drugs for AD targeting NF-κBsignaling cascade has been discussed in the end.

Nrf2–Keap1 pathway–mediated effects of resveratrol on oxidative stress and apoptosis in hydrogen peroxide–treated rheumatoid arthritis fibroblast‐like synoviocytes

“…Numerous studies have shown that NF‐κB is an important inflammatory transcriptional regulator that can be activated by oxidative stress . Under normal circumstances, NF‐κB is composed of multiple subunits in the cytoplasm.…”

Oxytocin in The Prevention of Injury Due to Testicular Torsion/Detorsion in Rats

“…[34,35] ROS overexpression secondary to oxidative stress can negatively affect proteins, lipids, nucleic acids, carbohydrates, and other molecules and leads to cell membrane lipid peroxidation, protein denaturation, DNA damage, inflammation, cell proliferation, cell dysfunction, and apoptosis. [36] Thus, ROS may play a role in the pathogenesis of several diseases, such as atherosclerosis, [37] cancer, [38] diabetes mellitus, [39] infection, [40] central nervous system disorders, [41] and testicular torsion due to its involvement in lipid peroxidation. [38] In addition, negative effects of oxidative stress on the testes after the initiation of reperfusion have been reported in the testicular torsion induced rat model.…”

Proteinopathy, oxidative stress and mitochondrial dysfunction: cross talk in Alzheimer's disease and Parkinson's disease

“…For example, the nature of the subunits binding to the NF-kB binding sites may determine whether up- or downregulation of BACE1 gene takes place 45. Similarly, though NF-kB is a redox-sensitive transcription factor, its interaction with ROS is complex and may lead to either activation and enhanced nuclear translocation in certain experimental conditions or decreased nuclear binding in others 48. However, oxidative stress-induced increased BACE1 activity has been reported in many experimental systems 46,49.…”