Normal and Pathological NRF2 Signalling in the Central Nervous System.

Fiche publication

Date publication

juillet 2022

Journal

Antioxidants (Basel, Switzerland)

Auteurs

Membres identifiés du Cancéropôle Est :
Dr BENANI Alexandre

Tous les auteurs :
Heurtaux T, Bouvier DS, Benani A, Helgueta Romero S, Frauenknecht KBM, Mittelbronn M, Sinkkonen L

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/35892629

Résumé

The nuclear factor erythroid 2-related factor 2 (NRF2) was originally described as a master regulator of antioxidant cellular response, but in the time since, numerous important biological functions linked to cell survival, cellular detoxification, metabolism, autophagy, proteostasis, inflammation, immunity, and differentiation have been attributed to this pleiotropic transcription factor that regulates hundreds of genes. After 40 years of in-depth research and key discoveries, NRF2 is now at the center of a vast regulatory network, revealing NRF2 signalling as increasingly complex. It is widely recognized that reactive oxygen species (ROS) play a key role in human physiological and pathological processes such as ageing, obesity, diabetes, cancer, and neurodegenerative diseases. The high oxygen consumption associated with high levels of free iron and oxidizable unsaturated lipids make the brain particularly vulnerable to oxidative stress. A good stability of NRF2 activity is thus crucial to maintain the redox balance and therefore brain homeostasis. In this review, we have gathered recent data about the contribution of the NRF2 pathway in the healthy brain as well as during metabolic diseases, cancer, ageing, and ageing-related neurodegenerative diseases. We also discuss promising therapeutic strategies and the need for better understanding of cell-type-specific functions of NRF2 in these different fields.