Normal and Pathological NRF2 Signalling in the Central Nervous System
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,...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-07-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/11/8/1426 |
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| author | Tony Heurtaux David S. Bouvier Alexandre Benani Sergio Helgueta Romero Katrin B. M. Frauenknecht Michel Mittelbronn Lasse Sinkkonen |
| author_facet | Tony Heurtaux David S. Bouvier Alexandre Benani Sergio Helgueta Romero Katrin B. M. Frauenknecht Michel Mittelbronn Lasse Sinkkonen |
| author_sort | Tony Heurtaux |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T10:02:11Z |
| format | Article |
| id | doaj.art-1e78c29d981d410a85847b40b822471a |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-09T10:02:11Z |
| publishDate | 2022-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-1e78c29d981d410a85847b40b822471a2023-12-01T23:19:49ZengMDPI AGAntioxidants2076-39212022-07-01118142610.3390/antiox11081426Normal and Pathological NRF2 Signalling in the Central Nervous SystemTony Heurtaux0David S. Bouvier1Alexandre Benani2Sergio Helgueta Romero3Katrin B. M. Frauenknecht4Michel Mittelbronn5Lasse Sinkkonen6Department of Life Sciences and Medicine (DLSM), University of Luxembourg, 4367 Belvaux, LuxembourgLuxembourg Center of Neuropathology (LCNP), 3555 Dudelange, LuxembourgCentre des Sciences du Goût et de l’Alimentation, AgroSup Dijon, CNRS, INRAE, Université Bourgogne Franche-Comté, 21000 Dijon, FranceDepartment of Life Sciences and Medicine (DLSM), University of Luxembourg, 4367 Belvaux, LuxembourgLuxembourg Center of Neuropathology (LCNP), 3555 Dudelange, LuxembourgDepartment of Life Sciences and Medicine (DLSM), University of Luxembourg, 4367 Belvaux, LuxembourgDepartment of Life Sciences and Medicine (DLSM), University of Luxembourg, 4367 Belvaux, LuxembourgThe 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.https://www.mdpi.com/2076-3921/11/8/1426NRF2reactive oxygen speciesglial cellsdietageingcancer |
| spellingShingle | Tony Heurtaux David S. Bouvier Alexandre Benani Sergio Helgueta Romero Katrin B. M. Frauenknecht Michel Mittelbronn Lasse Sinkkonen Normal and Pathological NRF2 Signalling in the Central Nervous System Antioxidants NRF2 reactive oxygen species glial cells diet ageing cancer |
| title | Normal and Pathological NRF2 Signalling in the Central Nervous System |
| title_full | Normal and Pathological NRF2 Signalling in the Central Nervous System |
| title_fullStr | Normal and Pathological NRF2 Signalling in the Central Nervous System |
| title_full_unstemmed | Normal and Pathological NRF2 Signalling in the Central Nervous System |
| title_short | Normal and Pathological NRF2 Signalling in the Central Nervous System |
| title_sort | normal and pathological nrf2 signalling in the central nervous system |
| topic | NRF2 reactive oxygen species glial cells diet ageing cancer |
| url | https://www.mdpi.com/2076-3921/11/8/1426 |
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