[en] Rheumatoid arthritis (RA) is an autoimmune disease with an important inflammatory component accompanied by deregulated redox-dependent signaling pathways that are feeding back into inflammation. In this context, we bring into focus the transcription factor NRF2, a master redox regulator that exerts exquisite antioxidant and anti-inflammatory effects. The review does not intend to be exhaustive, but to point out arguments sustaining the rationale for applying an NRF2-directed co-treatment in RA as well as its potential limitations. The involvement of NRF2 in RA is emphasized through an analysis of publicly available transcriptomic data on NRF2 target genes and the findings from NRF2-knockout mice. The impact of NRF2 on concurrent pathologic mechanisms in RA is explained by its crosstalk with major redox-sensitive inflammatory and cell death-related pathways, in the context of the increased survival of pathologic cells in RA. The proposed adjunctive therapy targeted to NRF2 is further sustained by the existence of promising NRF2 activators that are in various stages of drug development. The interference of NRF2 with conventional anti-rheumatic therapies is discussed, including the cytoprotective effects of NRF2 for alleviating drug toxicity. From another perspective, the review presents how NRF2 activation would be decreasing the efficacy of synthetic anti-rheumatic drugs by increasing drug efflux. Future perspectives regarding pharmacologic NRF2 activation in RA are finally proposed.
Precision for document type :
Review article
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Manda, Gina; Radiobiology Laboratory, Victor Babes National Institute of Pathology, Bucharest, Romania
Milanesi, Elena; Radiobiology Laboratory, Victor Babes National Institute of Pathology, Bucharest, Romania
Genc, Sermin; Neurodegeneration and Neuroprotection Laboratory, Izmir Biomedicine and Genome Center, Izmir, Turkey, Izmir International Biomedicine and Genome Institute, Dokuz Eylul University, Izmir, Turkey, Department of Neuroscience, Health Science Institute, Dokuz Eylul University, Izmir, Turkey
Niculite, Cristina Mariana; Radiobiology Laboratory, Victor Babes National Institute of Pathology, Bucharest, Romania, Department of Cellular and Molecular Biology and Histology, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
Neagoe, Ionela Victoria; Radiobiology Laboratory, Victor Babes National Institute of Pathology, Bucharest, Romania
TASTAN, Bora ; University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Neuroinflammation Group ; Neurodegeneration and Neuroprotection Laboratory, Izmir Biomedicine and Genome Center, Izmir, Turkey, Izmir International Biomedicine and Genome Institute, Dokuz Eylul University, Izmir, Turkey
Dragnea, Elena Mihaela; Radiobiology Laboratory, Victor Babes National Institute of Pathology, Bucharest, Romania
Cuadrado, Antonio ; 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: antonio.cuadrado@uam.es
External co-authors :
yes
Language :
English
Title :
Pros and cons of NRF2 activation as adjunctive therapy in rheumatoid arthritis.
The collaboration of the authors was supported by European COST Action CA20121 : Bench to bedside transition for pharmacological regulation of NRF2 in noncommunicable diseases (BenBedPhar). Webpage: https://benbedphar.org/about-benbedphar/ . GM, EM, CMN, IVN, EMD and AC were supported by the Romanian Ministry of Research, Innovation and Digitization through the European Regional Development Fund, Competitiveness Operational Program 2014–2020 [the REDBRAIN project, ID: P_37_732]. The authors thank to Dr. Andrei Constantinescu for revising the English language in the manuscript.The collaboration of the authors was supported by European COST Action CA20121: Bench to bedside transition for pharmacological regulation of NRF2 in noncommunicable diseases (BenBedPhar). Webpage: https://benbedphar.org/about-benbedphar/. GM, EM, CMN, IVN, EMD and AC were supported by the Romanian Ministry of Research, Innovation and Digitization through the European Regional Development Fund, Competitiveness Operational Program 2014–2020 [the REDBRAIN project, ID: P_37_732]. The authors thank to Dr. Andrei Constantinescu for revising the English language in the manuscript.
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