학술논문
Biomarkers of NRF2 signalling: Current status and future challenges
Document Type
article
Author
Christina Morgenstern; Isabel Lastres-Becker; Birsen Can Demirdöğen; 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
Source
Redox Biology, Vol 72, Iss , Pp 103134- (2024)
Subject
Language
English
ISSN
2213-2317
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.