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Tytuł:
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NRF2 as a therapeutic opportunity to impact in the molecular roadmap of ALS.
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Autorzy:
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Jiménez-Villegas J; Department of Biochemistry, Medical College, Autonomous University of Madrid (UAM), Madrid, Spain; Instituto de Investigaciones Biomédicas 'Alberto Sols' (CSIC-UAM), Madrid, Spain; Instituto de Investigación Sanitaria La Paz (IdiPaz), Madrid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain.
Ferraiuolo L; Sheffield Institute for Translational Neuroscience, University of Sheffield, Sheffield, UK.
Mead RJ; Sheffield Institute for Translational Neuroscience, University of Sheffield, Sheffield, UK.
Shaw PJ; Sheffield Institute for Translational Neuroscience, University of Sheffield, Sheffield, UK.
Cuadrado A; Department of Biochemistry, Medical College, Autonomous University of Madrid (UAM), Madrid, Spain; Instituto de Investigaciones Biomédicas 'Alberto Sols' (CSIC-UAM), Madrid, Spain; Instituto de Investigación Sanitaria La Paz (IdiPaz), Madrid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain.
Rojo AI; Department of Biochemistry, Medical College, Autonomous University of Madrid (UAM), Madrid, Spain; Instituto de Investigaciones Biomédicas 'Alberto Sols' (CSIC-UAM), Madrid, Spain; Instituto de Investigación Sanitaria La Paz (IdiPaz), Madrid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain. Electronic address: .
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Źródło:
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Free radical biology & medicine [Free Radic Biol Med] 2021 Sep; Vol. 173, pp. 125-141. Date of Electronic Publication: 2021 Jul 24.
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Typ publikacji:
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Journal Article; Research Support, Non-U.S. Gov't; Review
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Język:
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English
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Imprint Name(s):
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Publication: Tarrytown, NY : Elsevier Science
Original Publication: New York : Pergamon, c1987-
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MeSH Terms:
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Amyotrophic Lateral Sclerosis*/drug therapy
Amyotrophic Lateral Sclerosis*/genetics
NF-E2-Related Factor 2*/genetics
NF-E2-Related Factor 2*/metabolism
Antioxidants ; Gene Expression Regulation ; Humans ; Motor Neurons/metabolism
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Grant Information:
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BRC-1215-20017 United Kingdom DH_ Department of Health; MR/S004920/1 United Kingdom MRC_ Medical Research Council; NF-SI-0617-10077 United Kingdom DH_ Department of Health; MR/W00416X/1 United Kingdom MRC_ Medical Research Council; TURNER/OCT15/972-797 United Kingdom MNDA_ Motor Neurone Disease Association
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Contributed Indexing:
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Keywords: ALS molecular hallmarks; Amyotrophic lateral sclerosis; Clinical trials; Dysregulated pathways; NRF2; Therapy; Transcriptomic analysis
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Substance Nomenclature:
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0 (Antioxidants)
0 (NF-E2-Related Factor 2)
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Entry Date(s):
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Date Created: 20210727 Date Completed: 20210902 Latest Revision: 20230329
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Update Code:
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20240105
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DOI:
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10.1016/j.freeradbiomed.2021.07.022
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PMID:
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34314817
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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.
(Crown Copyright © 2021. Published by Elsevier Inc. All rights reserved.)