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Peripheral Blood NRF2 Expression as a Biomarker in Human Health and Disease

Nuclear factor erythroid 2-related factor 2 (NRF2), a transcription factor which plays a critical role in maintenance of cellular redox, has been identified as a therapeutic target in a number of human diseases. Several reports have demonstrated beneficial effects of NRF2 manipulation in animal mode...

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Autores principales: Neilson, Lee E., Quinn, Joseph F., Gray, Nora E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7824022/
https://www.ncbi.nlm.nih.gov/pubmed/33396641
http://dx.doi.org/10.3390/antiox10010028
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author Neilson, Lee E.
Quinn, Joseph F.
Gray, Nora E.
author_facet Neilson, Lee E.
Quinn, Joseph F.
Gray, Nora E.
author_sort Neilson, Lee E.
collection PubMed
description Nuclear factor erythroid 2-related factor 2 (NRF2), a transcription factor which plays a critical role in maintenance of cellular redox, has been identified as a therapeutic target in a number of human diseases. Several reports have demonstrated beneficial effects of NRF2 manipulation in animal models of disease, and one NRF2-activating drug, dimethyl fumarate, is already approved for the treatment of multiple sclerosis. However, drug discovery is slowed due to a dearth of biomarkers which can inform target engagement and magnitude and duration of action. Peripheral blood mononuclear cells (PBMCs) are an accessible, minimally-invasive source of biomarkers which can be readily assayed and objectively monitored as a surrogate endpoint of NRF2 activation in clinical trials. We undertook a review of the literature on PBMC NRF2 measurements in human studies to explore its role as a suitable biomarker in various contexts of health and disease. It is clear that NRF2 and its target genes can be readily assayed from PBMCs in multiple disease contexts and may track with disease progression. Further work needs to be undertaken to evaluate its stability but should be considered as an exploratory marker in clinical trials targeting NRF2 activation.
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spelling pubmed-78240222021-01-24 Peripheral Blood NRF2 Expression as a Biomarker in Human Health and Disease Neilson, Lee E. Quinn, Joseph F. Gray, Nora E. Antioxidants (Basel) Perspective Nuclear factor erythroid 2-related factor 2 (NRF2), a transcription factor which plays a critical role in maintenance of cellular redox, has been identified as a therapeutic target in a number of human diseases. Several reports have demonstrated beneficial effects of NRF2 manipulation in animal models of disease, and one NRF2-activating drug, dimethyl fumarate, is already approved for the treatment of multiple sclerosis. However, drug discovery is slowed due to a dearth of biomarkers which can inform target engagement and magnitude and duration of action. Peripheral blood mononuclear cells (PBMCs) are an accessible, minimally-invasive source of biomarkers which can be readily assayed and objectively monitored as a surrogate endpoint of NRF2 activation in clinical trials. We undertook a review of the literature on PBMC NRF2 measurements in human studies to explore its role as a suitable biomarker in various contexts of health and disease. It is clear that NRF2 and its target genes can be readily assayed from PBMCs in multiple disease contexts and may track with disease progression. Further work needs to be undertaken to evaluate its stability but should be considered as an exploratory marker in clinical trials targeting NRF2 activation. MDPI 2020-12-30 /pmc/articles/PMC7824022/ /pubmed/33396641 http://dx.doi.org/10.3390/antiox10010028 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Perspective
Neilson, Lee E.
Quinn, Joseph F.
Gray, Nora E.
Peripheral Blood NRF2 Expression as a Biomarker in Human Health and Disease
title Peripheral Blood NRF2 Expression as a Biomarker in Human Health and Disease
title_full Peripheral Blood NRF2 Expression as a Biomarker in Human Health and Disease
title_fullStr Peripheral Blood NRF2 Expression as a Biomarker in Human Health and Disease
title_full_unstemmed Peripheral Blood NRF2 Expression as a Biomarker in Human Health and Disease
title_short Peripheral Blood NRF2 Expression as a Biomarker in Human Health and Disease
title_sort peripheral blood nrf2 expression as a biomarker in human health and disease
topic Perspective
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7824022/
https://www.ncbi.nlm.nih.gov/pubmed/33396641
http://dx.doi.org/10.3390/antiox10010028
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