Jiménez-Villegas, J., Ferraiuolo, L. orcid.org/0000-0001-9118-5714, Mead, R.J. orcid.org/0000-0002-3207-0068 et al. (3 more authors) (2021) NRF2 as a therapeutic opportunity to impact in the molecular roadmap of ALS. Free Radical Biology and Medicine, 173. pp. 125-141. ISSN 0891-5849
Abstract
Amyotrophic Lateral Sclerosis (ALS) is a devastating heterogeneous disease with still no convincing therapy. To identify the most strategically significant hallmarks for therapeutic intervention, we have performed a comprehensive transcriptomics analysis of dysregulated pathways, comparing datasets from ALS patients and healthy donors. We have identified crucial alterations in RNA metabolism, intracellular transport, vascular system, redox homeostasis, proteostasis and inflammatory responses. Interestingly, the transcription factor NRF2 (nuclear factor (erythroid-derived 2)-like 2) has significant effects in modulating these pathways. NRF2 has been classically considered as the master regulator of the antioxidant cellular response, although it is currently considered as a key component of the transduction machinery to maintain coordinated control of protein quality, inflammation, and redox homeostasis. Herein, we will summarize the data from NRF2 activators in ALS pre-clinical models as well as those that are being studied in clinical trials. As we will discuss, NRF2 is a promising target to build a coordinated transcriptional response to motor neuron injury, highlighting its therapeutic potential to combat ALS.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | Crown Copyright © 2021 Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
Keywords: | NRF2; Amyotrophic lateral sclerosis; Therapy; Clinical trials; Dysregulated pathways; Transcriptomic analysis; ALS molecular hallmarks |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Sheffield Teaching Hospitals |
Funding Information: | Funder Grant number Medical Research Council MR/S004920/1; MR/V027735/1 |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 30 Jul 2021 12:58 |
Last Modified: | 30 Jul 2021 12:58 |
Status: | Published |
Publisher: | Elsevier BV |
Refereed: | Yes |
Identification Number: | 10.1016/j.freeradbiomed.2021.07.022 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:176682 |