Applications of the Keap1-Nrf2 system for gene and cell therapy

Free Radic Biol Med. 2015 Nov;88(Pt B):350-361. doi: 10.1016/j.freeradbiomed.2015.06.037. Epub 2015 Jul 8.

Abstract

Oxidative stress has been implicated to play a role in a number of acute and chronic diseases including acute injuries of the central nervous system, neurodegenerative and cardiovascular diseases, and cancer. The redox-activated transcription factor Nrf2 has been shown to protect many different cell types and organs from a variety of toxic insults, whereas in many cancers, unchecked Nrf2 activity increases the expression of cytoprotective genes and, consequently, provides growth advantage to cancerous cells. Herein, we discuss current preclinical gene therapy approaches to either increase or decrease Nrf2 activity with a special reference to neurological diseases and cancer. In addition, we discuss the role of Nrf2 in stem cell therapy for neurological disorders.

Keywords: Cancer; Gene therapy; Neurodegenerative diseases; Nrf2; Spinal cord injury; Stem cell therapy; Transcription factor.

Publication types

  • Review

MeSH terms

  • Animals
  • Genetic Therapy / methods*
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Intracellular Signaling Peptides and Proteins / metabolism
  • NF-E2-Related Factor 2 / genetics*
  • NF-E2-Related Factor 2 / metabolism
  • Neoplasms / therapy
  • Neurodegenerative Diseases / therapy
  • Oxidative Stress / physiology
  • Stem Cell Transplantation / methods*

Substances

  • Intracellular Signaling Peptides and Proteins
  • NF-E2-Related Factor 2