Biomarkers of NRF2 signalling: Current status and future challenges

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...

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Detalles Bibliográficos
Autores: 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, I. P., Piechota-Polanczyk, Aleksandra, Mickael, Michel-Edwar, Santos, Marlene, Kensler, Thomas W., Cuadrado, Antonio, Copple, Ian M.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2024
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/371261
Acceso en línea:http://hdl.handle.net/10261/371261
Access Level:acceso abierto
Palabra clave:NRF2
Transcription factor
Target genes
Biomarker
Oxidative stress response
Descripción
Sumario: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.