Biomarkers of NRF2 Signalling: Current Status and Future Challenges

Overview

Journal Redox Biol

Specialties Biology
Cell Biology
Endocrinology

Date 2024 Apr 21

PMID 38643749

Authors

Christina Morgenstern

Isabel Lastres-Becker

Birsen Can Demirdogen

Vera Marisa Costa

Andreas Daiber

Roberta Foresti

Roberto Motterlini

Sibel Kalyoncu

Burak I Arioz

Sermin Genc

Monika Jakubowska

Ioannis P Trougakos

Aleksandra Piechota-Polanczyk

Michel Mickael

Marlene Santos

Thomas W Kensler

Antonio Cuadrado

Ian M Copple

Affiliations

Soon will be listed here.

Abstract

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.

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