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Activators and Inhibitors of NRF2: A Review of Their Potential for Clinical Development

Natalia Robledinos-Antón1,2, Raquel Fernández-Ginés1,2, Gina Manda3

  • 1Instituto de Investigaciones Biomédicas "Alberto Sols" UAM-CSIC, Instituto de Investigación Sanitaria La Paz (IdiPaz) and Department of Biochemistry, Faculty of Medicine, Autonomous University of Madrid, Madrid, Spain.

Oxidative Medicine and Cellular Longevity
|August 10, 2019
PubMed

Insights

Nuclear factor erythroid 2-related factor 2 (NRF2) activation shows therapeutic potential for chronic diseases linked to oxidative stress. Conversely, NRF2 inhibition is explored for cancer therapy, targeting tumor survival.

Area of Science:

  • Molecular Biology
  • Biochemistry
  • Pharmacology

Background:

  • Nuclear factor erythroid 2-related factor 2 (NRF2) is a key transcription factor regulating cellular responses to stress.
  • NRF2 activation protects against oxidative stress and inflammation, implicated in chronic diseases.
  • In cancer, NRF2 promotes tumor cell survival, making its inhibition a therapeutic target.

Purpose of the Study:

  • To review NRF2 activators with clinical potential for chronic diseases.
  • To analyze the current status of NRF2 inhibitors for cancer therapy.

Main Methods:

  • Literature review of NRF2 activators (electrophilic and nonelectrophilic).
  • Analysis of NRF2 inhibitors and their role in cancer therapy.

Main Results:

  • NRF2 activators are promising for treating neurodegenerative, cardiovascular, and metabolic diseases.
  • NRF2 inhibitors have demonstrated proof of concept for blocking NRF2 in cancer.

Conclusions:

  • Pharmacological modulation of NRF2 offers dual therapeutic strategies: activation for chronic diseases and inhibition for cancer.
  • Further research into NRF2 pathways could yield novel treatments for a range of conditions.

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