Model organisms for investigating the functional involvement of NRF2 in non-communicable diseases

Ana I. Rojo; Brigitta Buttari; Susana Cadenas; Ana Rita Carlos; Antonio Cuadrado; Ana Sofia Falcão; Manuela G. López; Milen I. Georgiev; Anna Grochot-Przeczek; Sentiljana Gumeni; José Jimenez-Villegas; Jarosław Olav Horbanczuk; Ozlen Konu; Isabel Lastres-Becker; Anna Liisa Levonen; Viktorija Maksimova; Charalambos Michaeloudes; Liliya V. Mihaylova; Michel Edwar Mickael; Irina Milisav; Biljana Miova; Patricia Rada; Marlene Santos; Miguel C. Seabra; Dubravka Svob Strac; Sandra Tenreiro; Ioannis P. Trougakos; Albena T. Dinkova-Kostova

doi:10.1016/j.redox.2024.103464

Model organisms for investigating the functional involvement of NRF2 in non-communicable diseases

Ana I. Rojo (Lead / Corresponding author)
, Brigitta Buttari
, Susana Cadenas
, Ana Rita Carlos
, Antonio Cuadrado
, Ana Sofia Falcão
, Manuela G. López
, Milen I. Georgiev
, Anna Grochot-Przeczek
, Sentiljana Gumeni
, José Jimenez-Villegas
, Jarosław Olav Horbanczuk
, Ozlen Konu
, Isabel Lastres-Becker
, Anna Liisa Levonen
, Viktorija Maksimova
, Charalambos Michaeloudes
, Liliya V. Mihaylova
, Michel Edwar Mickael
, Irina Milisav

Biljana Miova, Patricia Rada, Marlene Santos, Miguel C. Seabra, Dubravka Svob Strac, Sandra Tenreiro, Ioannis P. Trougakos, Albena T. Dinkova-Kostova

MED Cancer Research

Research output: Contribution to journal › Review article › peer-review

13 Citations (Scopus)

201 Downloads (Pure)

Abstract

Non-communicable chronic diseases (NCDs) are most commonly characterized by age-related loss of homeostasis and/or by cumulative exposures to environmental factors, which lead to low-grade sustained generation of reactive oxygen species (ROS), chronic inflammation and metabolic imbalance. Nuclear factor erythroid 2-like 2 (NRF2) is a basic leucine-zipper transcription factor that regulates the cellular redox homeostasis. NRF2 controls the expression of more than 250 human genes that share in their regulatory regions a cis-acting enhancer termed the antioxidant response element (ARE). The products of these genes participate in numerous functions including biotransformation and redox homeostasis, lipid and iron metabolism, inflammation, proteostasis, as well as mitochondrial dynamics and energetics. Thus, it is possible that a single pharmacological NRF2 modulator might mitigate the effect of the main hallmarks of NCDs, including oxidative, proteostatic, inflammatory and/or metabolic stress. Research on model organisms has provided tremendous knowledge of the molecular mechanisms by which NRF2 affects NCDs pathogenesis. This review is a comprehensive summary of the most commonly used model organisms of NCDs in which NRF2 has been genetically or pharmacologically modulated, paving the way for drug development to combat NCDs. We discuss the validity and use of these models and identify future challenges.

Original language	English
Article number	103464
Number of pages	52
Journal	Redox Biology
Volume	79
Early online date	16 Dec 2024
DOIs	https://doi.org/10.1016/j.redox.2024.103464
Publication status	Published - Feb 2025

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Inflammation
Model organisms
Non-communicable chronic diseases
NRF2
Oxidative stress

ASJC Scopus subject areas

Organic Chemistry

Access to Document

10.1016/j.redox.2024.103464Licence: CC BY-NC-ND

Final published versionFinal published version, 9.58 MBLicence: CC BY-NC-ND

Cite this

Rojo, A. I., Buttari, B., Cadenas, S., Carlos, A. R., Cuadrado, A., Falcão, A. S., López, M. G., Georgiev, M. I., Grochot-Przeczek, A., Gumeni, S., Jimenez-Villegas, J., Horbanczuk, J. O., Konu, O., Lastres-Becker, I., Levonen, A. L., Maksimova, V., Michaeloudes, C., Mihaylova, L. V., Mickael, M. E., ... Dinkova-Kostova, A. T. (2025). Model organisms for investigating the functional involvement of NRF2 in non-communicable diseases. Redox Biology, 79, Article 103464. https://doi.org/10.1016/j.redox.2024.103464

@article{21e40c918b82430c9e2838a5409fba9c,

title = "Model organisms for investigating the functional involvement of NRF2 in non-communicable diseases",

abstract = "Non-communicable chronic diseases (NCDs) are most commonly characterized by age-related loss of homeostasis and/or by cumulative exposures to environmental factors, which lead to low-grade sustained generation of reactive oxygen species (ROS), chronic inflammation and metabolic imbalance. Nuclear factor erythroid 2-like 2 (NRF2) is a basic leucine-zipper transcription factor that regulates the cellular redox homeostasis. NRF2 controls the expression of more than 250 human genes that share in their regulatory regions a cis-acting enhancer termed the antioxidant response element (ARE). The products of these genes participate in numerous functions including biotransformation and redox homeostasis, lipid and iron metabolism, inflammation, proteostasis, as well as mitochondrial dynamics and energetics. Thus, it is possible that a single pharmacological NRF2 modulator might mitigate the effect of the main hallmarks of NCDs, including oxidative, proteostatic, inflammatory and/or metabolic stress. Research on model organisms has provided tremendous knowledge of the molecular mechanisms by which NRF2 affects NCDs pathogenesis. This review is a comprehensive summary of the most commonly used model organisms of NCDs in which NRF2 has been genetically or pharmacologically modulated, paving the way for drug development to combat NCDs. We discuss the validity and use of these models and identify future challenges.",

keywords = "Inflammation, Model organisms, Non-communicable chronic diseases, NRF2, Oxidative stress",

author = "Rojo, \{Ana I.\} and Brigitta Buttari and Susana Cadenas and Carlos, \{Ana Rita\} and Antonio Cuadrado and Falc{\~a}o, \{Ana Sofia\} and L{\'o}pez, \{Manuela G.\} and Georgiev, \{Milen I.\} and Anna Grochot-Przeczek and Sentiljana Gumeni and Jos{\'e} Jimenez-Villegas and Horbanczuk, \{Jaros{\l}aw Olav\} and Ozlen Konu and Isabel Lastres-Becker and Levonen, \{Anna Liisa\} and Viktorija Maksimova and Charalambos Michaeloudes and Mihaylova, \{Liliya V.\} and Mickael, \{Michel Edwar\} and Irina Milisav and Biljana Miova and Patricia Rada and Marlene Santos and Seabra, \{Miguel C.\} and Strac, \{Dubravka Svob\} and Sandra Tenreiro and Trougakos, \{Ioannis P.\} and Dinkova-Kostova, \{Albena T.\}",

note = "Publisher Copyright: {\textcopyright} 2024 The Authors",

year = "2025",

month = feb,

doi = "10.1016/j.redox.2024.103464",

language = "English",

volume = "79",

journal = "Redox Biology",

issn = "2213-2317",

publisher = "Elsevier",

}

Rojo, AI, Buttari, B, Cadenas, S, Carlos, AR, Cuadrado, A, Falcão, AS, López, MG, Georgiev, MI, Grochot-Przeczek, A, Gumeni, S, Jimenez-Villegas, J, Horbanczuk, JO, Konu, O, Lastres-Becker, I, Levonen, AL, Maksimova, V, Michaeloudes, C, Mihaylova, LV, Mickael, ME, Milisav, I, Miova, B, Rada, P, Santos, M, Seabra, MC, Strac, DS, Tenreiro, S, Trougakos, IP & Dinkova-Kostova, AT 2025, 'Model organisms for investigating the functional involvement of NRF2 in non-communicable diseases', Redox Biology, vol. 79, 103464. https://doi.org/10.1016/j.redox.2024.103464

TY - JOUR

T1 - Model organisms for investigating the functional involvement of NRF2 in non-communicable diseases

AU - Rojo, Ana I.

AU - Buttari, Brigitta

AU - Cadenas, Susana

AU - Carlos, Ana Rita

AU - Cuadrado, Antonio

AU - Falcão, Ana Sofia

AU - López, Manuela G.

AU - Georgiev, Milen I.

AU - Grochot-Przeczek, Anna

AU - Gumeni, Sentiljana

AU - Jimenez-Villegas, José

AU - Horbanczuk, Jarosław Olav

AU - Konu, Ozlen

AU - Lastres-Becker, Isabel

AU - Levonen, Anna Liisa

AU - Maksimova, Viktorija

AU - Michaeloudes, Charalambos

AU - Mihaylova, Liliya V.

AU - Mickael, Michel Edwar

AU - Milisav, Irina

AU - Miova, Biljana

AU - Rada, Patricia

AU - Santos, Marlene

AU - Seabra, Miguel C.

AU - Strac, Dubravka Svob

AU - Tenreiro, Sandra

AU - Trougakos, Ioannis P.

AU - Dinkova-Kostova, Albena T.

PY - 2025/2

Y1 - 2025/2

N2 - Non-communicable chronic diseases (NCDs) are most commonly characterized by age-related loss of homeostasis and/or by cumulative exposures to environmental factors, which lead to low-grade sustained generation of reactive oxygen species (ROS), chronic inflammation and metabolic imbalance. Nuclear factor erythroid 2-like 2 (NRF2) is a basic leucine-zipper transcription factor that regulates the cellular redox homeostasis. NRF2 controls the expression of more than 250 human genes that share in their regulatory regions a cis-acting enhancer termed the antioxidant response element (ARE). The products of these genes participate in numerous functions including biotransformation and redox homeostasis, lipid and iron metabolism, inflammation, proteostasis, as well as mitochondrial dynamics and energetics. Thus, it is possible that a single pharmacological NRF2 modulator might mitigate the effect of the main hallmarks of NCDs, including oxidative, proteostatic, inflammatory and/or metabolic stress. Research on model organisms has provided tremendous knowledge of the molecular mechanisms by which NRF2 affects NCDs pathogenesis. This review is a comprehensive summary of the most commonly used model organisms of NCDs in which NRF2 has been genetically or pharmacologically modulated, paving the way for drug development to combat NCDs. We discuss the validity and use of these models and identify future challenges.

AB - Non-communicable chronic diseases (NCDs) are most commonly characterized by age-related loss of homeostasis and/or by cumulative exposures to environmental factors, which lead to low-grade sustained generation of reactive oxygen species (ROS), chronic inflammation and metabolic imbalance. Nuclear factor erythroid 2-like 2 (NRF2) is a basic leucine-zipper transcription factor that regulates the cellular redox homeostasis. NRF2 controls the expression of more than 250 human genes that share in their regulatory regions a cis-acting enhancer termed the antioxidant response element (ARE). The products of these genes participate in numerous functions including biotransformation and redox homeostasis, lipid and iron metabolism, inflammation, proteostasis, as well as mitochondrial dynamics and energetics. Thus, it is possible that a single pharmacological NRF2 modulator might mitigate the effect of the main hallmarks of NCDs, including oxidative, proteostatic, inflammatory and/or metabolic stress. Research on model organisms has provided tremendous knowledge of the molecular mechanisms by which NRF2 affects NCDs pathogenesis. This review is a comprehensive summary of the most commonly used model organisms of NCDs in which NRF2 has been genetically or pharmacologically modulated, paving the way for drug development to combat NCDs. We discuss the validity and use of these models and identify future challenges.

KW - Inflammation

KW - Model organisms

KW - Non-communicable chronic diseases

KW - NRF2

KW - Oxidative stress

UR - https://www.scopus.com/pages/publications/85212535347

U2 - 10.1016/j.redox.2024.103464

DO - 10.1016/j.redox.2024.103464

M3 - Review article

C2 - 39709790

AN - SCOPUS:85212535347

SN - 2213-2317

VL - 79

JO - Redox Biology

JF - Redox Biology

M1 - 103464

ER -

Model organisms for investigating the functional involvement of NRF2 in non-communicable diseases

Abstract

UN SDGs

Keywords

ASJC Scopus subject areas

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The Role of Nrf2 in the Tumour Microenvironment of IDH Wild-Type Glioma (Joint with University of Edinburgh)

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Model organisms for investigating the functional involvement of NRF2 in non-communicable diseases

Abstract

UN SDGs

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Projects

The Role of Nrf2 in the Tumour Microenvironment of IDH Wild-Type Glioma (Joint with University of Edinburgh)

Cite this