Browsing by Author "Lastres-Becker, Isabel"
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- Biomarkers of NRF2 signalling: Current status and future challengesPublication . Morgenstern, Christina; Lastres-Becker, Isabel; Demirdöğen, Birsen Can; Costa, Vera Marisa; Daiber, Andreas; Foresti, Roberta; Motterlini, Roberto; Kalyoncu, Sibel; Arioz, Burak I.; Genc, Sermin; Jakubowska, Monika; Trougakos, Ioannis P.; Piechota-Polanczyk, Aleksandra; Mickael, Michel; Santos, Marlene; Kensler, Thomas W.; Cuadrado, Antonio; Copple, Ian M.The cytoprotective transcription factor NRF2 regulates the expression of several hundred genes in mammalian cells and is a promising therapeutic target in a number of diseases associated with oxidative stress and inflammation. Hence, an ability to monitor basal and inducible NRF2 signalling is vital for mechanistic understanding in translational studies. Due to some caveats related to the direct measurement of NRF2 levels, the modulation of NRF2 activity is typically determined by measuring changes in the expression of one or more of its target genes and/or the associated protein products. However, there is a lack of consensus regarding the most relevant set of these genes/proteins that best represents NRF2 activity across cell types and species. We present the findings of a comprehensive literature search that according to stringent criteria identifies GCLC, GCLM, HMOX1, NQO1, SRXN1 and TXNRD1 as a robust panel of markers that are directly regulated by NRF2 in multiple cell and tissue types. We assess the relevance of these markers in clinically accessible biofluids and highlight future challenges in the development and use of NRF2 biomarkers in humans.
- Model organisms for investigating the functional involvement of NRF2 in non-communicable diseasesPublication . Rojo, Ana I.; Buttari, Brigitta; Cadenas, Susana; Carlos, Ana Rita; Cuadrado, Antonio; Falcão, Ana Sofia; López, Manuela G.; Georgiev, Milen I.; Grochot-Przeczek, Anna; Gumeni, Sentiljana; Jimenez-Villegas, José; Horbanczuk, Jarosław Olav; Konu, Ozlen; Lastres-Becker, Isabel; Levonen, Anna-Liisa; Maksimova, Viktorija; Michaeloudes, Charalambos; Mihaylova, Liliya V.; Mickael, Michel Edwar; Milisav, Irina; Miova, Biljana; Rada, Patricia; Santos, Marlene; Seabra, Miguel C.; Strac, Dubravka Svob; Tenreiro, Sandra; Trougakos, Ioannis P.; Dinkova-Kostova, Albena T.Non-communicable chronic diseases (NCDs) are most commonly characterized by agerelated 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.