Browsing by Author "Morgenstern, Christina"
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- Altered NRF2 signalling in systemic redox imbalance: Insights from non-communicable diseasesPublication . Santos, Marlene; Morgenstern, Christina; Santos, MarleneThe balanced activity of the cytoprotective transcription factor NRF2 is central for maintaining redox, metabolic-energetics, and proteome homeostasis, as well as for regulating inflammatory responses, among other functions. Activated NRF2 regulates the expression of hundreds of genes containing antioxidant response elements (AREs) or electrophile response elements (EpRE) in their regulatory regions, often promoting cytoprotection under stress conditions and contributing to defence against various pathologies and non-communicable diseases (NCDs). The products of increased NRF2 activity, detected systemically, may originate from either the white blood cells, the cells of the vasculature or tissue-derived products that could be secreted into biological fluids. Therefore, assessing basal and inducible NRF2 activity in blood or other biofluids is crucial for inferring NRF2 responses in local and often inaccessible tissues. In previous work, we identified a panel of six biomarkers - Glutamate-cysteine ligase catalytic subunit (GCLC), Glutamate-cysteine ligase modifier subunit (GCLM), Haem oxygenase 1 (HMOX1), NAD(P)H quinone dehydrogenase 1 (NQO1), Sulfiredoxin 1 (SRXN1), and Thioredoxin reductase 1 (TXNRD1) - as indicators of NRF2 activity. In the current study, we assess their utility in a clinical setting to measure NRF2 activation in a disease context. Here we discuss findings on how NRF2 activity in accessible human samples can reveal its involvement in various NCDs and its connection to clinical aspects such as diagnosis, disease progression and response to therapy.
- 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.