TY - JOUR
T1 - Normal and Pathological NRF2 Signalling in the Central Nervous System
AU - Heurtaux, Tony
AU - Bouvier, David S.
AU - Benani, Alexandre
AU - Helgueta Romero, Sergio
AU - Frauenknecht, Katrin B.M.
AU - Mittelbronn, Michel
AU - Sinkkonen, Lasse
N1 - Funding Information:
S.H.R. is supported by Fonds National de Recherche de Luxembourg (FNR)-PRIDE (PRIDE17/12244779/PARK-Q); L.S. has received funding from FNR, Fondation du Pélican de Mie et Pierre Hippert-Faber, Luxembourg Rotary Foundation, Luxembourg Personalized Medicine Consortium, and University of Luxembourg Internal Research Project grants; M.M. would like to thank the FNR for the support (PEARL P16/BM/11192868 grant).
Publisher Copyright:
© 2022 by the authors.
PY - 2022/7/22
Y1 - 2022/7/22
N2 - 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.
AB - 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.
KW - ageing
KW - cancer
KW - diet
KW - epigenetic regulation
KW - glial cells
KW - neurodegeneration
KW - NRF2
KW - reactive oxygen species
UR - http://www.scopus.com/inward/record.url?scp=85137316498&partnerID=8YFLogxK
UR - https://pubmed.ncbi.nlm.nih.gov/35892629
U2 - 10.3390/antiox11081426
DO - 10.3390/antiox11081426
M3 - Review article
C2 - 35892629
SN - 2076-3921
VL - 11
JO - Antioxidants
JF - Antioxidants
IS - 8
M1 - 1426
ER -