Model organisms for investigating the functional involvement of NRF2 in non-communicable diseases
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 fa...
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Elsevier
2025-02-01
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| Series: | Redox Biology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213231724004427 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Ana I. Rojo |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-ae67d14854ca42e8b443753093f7e796 |
| institution | OA Journals |
| issn | 2213-2317 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Redox Biology |
| spelling | doaj-art-ae67d14854ca42e8b443753093f7e7962025-08-20T02:34:40ZengElsevierRedox Biology2213-23172025-02-017910346410.1016/j.redox.2024.103464Model organisms for investigating the functional involvement of NRF2 in non-communicable diseasesAna I. Rojo0Brigitta Buttari1Susana Cadenas2Ana Rita Carlos3Antonio Cuadrado4Ana Sofia Falcão5Manuela G. López6Milen I. Georgiev7Anna Grochot-Przeczek8Sentiljana Gumeni9José Jimenez-Villegas10Jarosław Olav Horbanczuk11Ozlen Konu12Isabel Lastres-Becker13Anna-Liisa Levonen14Viktorija Maksimova15Charalambos Michaeloudes16Liliya V. Mihaylova17Michel Edwar Mickael18Irina Milisav19Biljana Miova20Patricia Rada21Marlene Santos22Miguel C. Seabra23Dubravka Svob Strac24Sandra Tenreiro25Ioannis P. Trougakos26Albena T. Dinkova-Kostova27Department of Biochemistry, Medical College, Autonomous University of Madrid (UAM), Madrid, Spain; Instituto de Investigación Sanitaria La Paz (IdiPaz), Madrid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain; Instituto de Investigaciones Biomédicas Sols-Morreale (CSIC-UAM), Madrid, Spain; Corresponding author. Instituto de Investigaciones Biomédicas ''Sols-Morreale'', C/Arturo Duperier, 4. 28029, Madrid, Spain.Department of Cardiovascular, Endocrine-Metabolic Diseases, and Aging, Italian National Institute of Health, 00161, Rome, ItalyCentro de Biología Molecular Severo Ochoa (CSIC/UAM), Cantoblanco, Madrid, SpainCE3C-CHANGE, Department of Animal Biology, Faculty of Sciences, University of Lisbon, 1749-016, Lisbon, PortugalDepartment of Biochemistry, Medical College, Autonomous University of Madrid (UAM), Madrid, Spain; Instituto de Investigación Sanitaria La Paz (IdiPaz), Madrid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain; Instituto de Investigaciones Biomédicas Sols-Morreale (CSIC-UAM), Madrid, SpainiNOVA4Health, NOVA Medical School|Faculdade de Ciências Médicas, NMS|FCM, Universidade NOVA de Lisboa, Lisboa, PortugalDepartamento de Farmacología y Terapéutica, Facultad de Medicina, Universidad Autónoma de Madrid, Madrid, Spain; Instituto de Investigación Sanitaria La Princesa, Hospital Universitario de la Princesa, Madrid, SpainDepartment of Plant Cell Biotechnology, Center of Plant Systems Biology and Biotechnology, 4000, Plovdiv, Bulgaria; Laboratory of Metabolomics, Institute of Microbiology, Bulgarian Academy of Sciences, 139 Ruski Blvd., 4000, Plovdiv, BulgariaDepartment of Medical Biotechnology, Faculty of Biochemistry Biophysics and Biotechnology, Jagiellonian University, 30-387, Krakow, PolandDepartment of Cell Biology and Biophysics, Faculty of Biology, National and Kapodistrian University of Athens, Athens, 15784, GreeceDepartment of Biochemistry, Medical College, Autonomous University of Madrid (UAM), Madrid, Spain; Instituto de Investigación Sanitaria La Paz (IdiPaz), Madrid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain; Instituto de Investigaciones Biomédicas Sols-Morreale (CSIC-UAM), Madrid, SpainDepartment of Experimental Genomics, Institute of Genetics and Animal Biotechnology, 36A Postępu, Jastrzębiec, 05-552, PolandDepartment of Molecular Biology and Genetics, Bilkent University, Ankara, Turkey; Department of Neuroscience, Bilkent University, Ankara, Turkey; UNAM-Institute of Materials Science and Nanotechnology, Bilkent University, Ankara, TurkeyDepartment of Biochemistry, Medical College, Autonomous University of Madrid (UAM), Madrid, Spain; Instituto de Investigación Sanitaria La Paz (IdiPaz), Madrid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain; Institute Teófilo Hernando for Drug Discovery, Universidad Autónoma de Madrid, 28029, Madrid, Spain; Instituto de Investigaciones Biomédicas Sols-Morreale (CSIC-UAM), Madrid, SpainA.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, P.O. Box 1627, FI-70210, Kuopio, FinlandDepartment of Applied Pharmacy, Division of Pharmacy, Faculty of Medical Sciences, Goce Delcev University, Stip, Krste Misirkov Str., No. 10-A, P.O. Box 201, 2000, Stip, MacedoniaSchool of Medicine, European University Cyprus, Nicosia, CyprusDepartment of Plant Cell Biotechnology, Center of Plant Systems Biology and Biotechnology, 4000, Plovdiv, Bulgaria; Laboratory of Metabolomics, Institute of Microbiology, Bulgarian Academy of Sciences, 139 Ruski Blvd., 4000, Plovdiv, BulgariaDepartment of Experimental Genomics, Institute of Genetics and Animal Biotechnology, 36A Postępu, Jastrzębiec, 05-552, PolandInstitute of Pathophysiology, Faculty of Medicine, University of Ljubljana, Zaloska 4, 1000, Ljubljana, Slovenia; Laboratory of oxidative stress research, Faculty of Health Sciences, University of Ljubljana, Zdravstvena pot 5, 1000, Ljubljana, SloveniaDepartment of Experimental Physiology and Biochemistry, Institute of Biology, Faculty of Natural Sciences and Mathematics, University ''St Cyril and Methodius'', Skopje, MacedoniaInstituto de Investigaciones Biomédicas Sols-Morreale (IIBM), Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid, Madrid, Spain; Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Madrid, SpainREQUIMTE/LAQV, Escola Superior de Saúde (E2S), Instituto Politécnico do Porto, Rua Dr. António Bernardino de Almeida 400, 4200-072, Porto, Portugal; Molecular Oncology & Viral Pathology, IPO-Porto Research Center (CI-IPOP), Portuguese Institute of Oncology, 4200-072, Porto, PortugaliNOVA4Health, NOVA Medical School|Faculdade de Ciências Médicas, NMS|FCM, Universidade NOVA de Lisboa, Lisboa, PortugalLaboratory for Molecular Neuropsychiatry, Division of Molecular Medicine, Ruder Boskovic Institute, 10 000, Zagreb, CroatiaiNOVA4Health, NOVA Medical School|Faculdade de Ciências Médicas, NMS|FCM, Universidade NOVA de Lisboa, Lisboa, PortugalDepartment of Cell Biology and Biophysics, Faculty of Biology, National and Kapodistrian University of Athens, Athens, 15784, GreeceJacqui Wood Cancer Centre, Division of Cancer Research, School of Medicine, University of Dundee, Dundee, UK; Department of Pharmacology and Molecular Sciences and Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USANon-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.http://www.sciencedirect.com/science/article/pii/S2213231724004427InflammationModel organismsNon-communicable chronic diseasesNRF2Oxidative stress |
| spellingShingle | 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 Model organisms for investigating the functional involvement of NRF2 in non-communicable diseases Redox Biology Inflammation Model organisms Non-communicable chronic diseases NRF2 Oxidative stress |
| title | Model organisms for investigating the functional involvement of NRF2 in non-communicable diseases |
| title_full | Model organisms for investigating the functional involvement of NRF2 in non-communicable diseases |
| title_fullStr | Model organisms for investigating the functional involvement of NRF2 in non-communicable diseases |
| title_full_unstemmed | Model organisms for investigating the functional involvement of NRF2 in non-communicable diseases |
| title_short | Model organisms for investigating the functional involvement of NRF2 in non-communicable diseases |
| title_sort | model organisms for investigating the functional involvement of nrf2 in non communicable diseases |
| topic | Inflammation Model organisms Non-communicable chronic diseases NRF2 Oxidative stress |
| url | http://www.sciencedirect.com/science/article/pii/S2213231724004427 |
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