Reactive oxygen species, redox signaling and neuroinflammation in Alzheimer's disease: the NF-κB connection

Curr Top Med Chem. 2015;15(5):446-57. doi: 10.2174/1568026615666150114160543.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / metabolism
  • Alzheimer Disease / pathology
  • Amyloid beta-Peptides / antagonists & inhibitors*
  • Amyloid beta-Peptides / metabolism
  • Animals
  • Antioxidants / chemical synthesis*
  • Antioxidants / therapeutic use
  • Brain / drug effects
  • Brain / metabolism
  • Brain / pathology
  • Curcumin / pharmacology
  • Cytokines / antagonists & inhibitors
  • Cytokines / genetics
  • Cytokines / metabolism
  • Diterpenes, Kaurane / pharmacology
  • Gene Expression Regulation
  • Humans
  • Mice
  • NF-kappa B / antagonists & inhibitors*
  • NF-kappa B / genetics
  • NF-kappa B / metabolism
  • Neuroprotective Agents / chemical synthesis*
  • Neuroprotective Agents / therapeutic use
  • Oxidative Stress / drug effects
  • Reactive Oxygen Species / antagonists & inhibitors
  • Reactive Oxygen Species / metabolism
  • Signal Transduction / drug effects

Substances

  • Amyloid beta-Peptides
  • Antioxidants
  • Cytokines
  • Diterpenes, Kaurane
  • NF-kappa B
  • Neuroprotective Agents
  • Reactive Oxygen Species
  • oridonin
  • Curcumin