A Pivotal Role of the Nrf2 Signaling Pathway in Spinal Cord Injury: A Prospective Therapeutics Study

CNS Neurol Disord Drug Targets. 2020;19(3):207-219. doi: 10.2174/1871527319666200604175118.

Abstract

The nuclear erythroid 2-related factor 2 (Nrf2) signaling pathway has a main role against oxidative stress and inflammation. Spinal Cord Injury (SCI) leads to the high secretion of inflammatory cytokines and reactive oxygen species, which disturbs nervous system function and regeneration. Several studies have indicated that the activation of the Nrf2 signaling pathway may be effective against inflammation after SCI. The experimental studies have indicated that many chemical and natural agents act as Nrf2 inducer, which inhibits the SCI progression. Thus, the finding of novel Nrf2- inducer anti-inflammatory agents may be a valuable approach in drug discovery. In the present review, we discussed the Nrf2 signal pathway and crosstalk with the NF-κB pathway and also the impact of this pathway on inflammation in animal models of SCI. Furthermore, we discussed the regulation of Nrf2 by several phytochemicals and drugs, as well as their effects on the SCI inhibition. Therefore, the current study presented a new hypothesis of the development of anti-inflammatory agents that mediate the Nrf2 signaling pathway for treating the SCI outcomes.

Keywords: Inflammation; NQO-1; Nrf2; nervous system; oxidative stress; spinal cord injury.

Publication types

  • Review

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / therapeutic use
  • Cytokines / metabolism
  • Inflammation / drug therapy
  • NF-E2-Related Factor 2 / metabolism*
  • NF-kappa B / metabolism
  • Oxidative Stress / physiology
  • Prospective Studies
  • Signal Transduction / drug effects
  • Spinal Cord Injuries / metabolism*

Substances

  • Anti-Inflammatory Agents
  • Cytokines
  • NF-E2-Related Factor 2
  • NF-kappa B
  • NFE2L2 protein, human