Evidence map›Paper›PMID 39858508›Full record

ReviewBiomolecules2025

Proteostasis Decline and Redox Imbalance in Age-Related Diseases: The Therapeutic Potential of NRF2.

Brigitta Buttari, Antonella Tramutola, Ana I Rojo, Niki Chondrogianni, Sarmistha Saha, Alessandra Berry, Letizia Giona, Joana P Miranda, Elisabetta Profumo, Sergio Davinelli and 3 more

Abstract readReview
In one paragraph

Review in Biomolecules, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

28 citing papers in PubMed.

  1. Article
  2. Aloin attenuates high-glucose-induced oxidative and inflammatory damage in renal cells via AMPK/Nrf2 signaling.Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences · 2026
    Article
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  8. Article
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  14. Hops (Nutrients · 2026
    Article
  15. Physiological responses to mask-associated COFrontiers in public health · 2026
    Review
  16. Review
  17. Article
  18. Review
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  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors.

Brigitta ButtariDepartment of Cardiovascular and Endocrine-Metabolic Diseases and Aging, Istituto Superiore di Sanità, 00161 Rome, Italy.ORCID 0000-0002-0575-4106
Antonella TramutolaDepartment of Biochemical Sciences "A. Rossi Fanelli", Sapienza University, 00185 Rome, Italy.ORCID 0000-0002-9564-2086
Ana I RojoDepartment of Biochemistry, Faculty of Medicine, Autonomous University of Madrid, Centro de Investigación Biomédica en Red Sobre Enfermedades Neurodegenerativas (CIBERNED), National Institute of Health Carlos III (ISCIII), Instituto de Investigación Sanitaria La Paz (IdiPaz), 28049 Madrid, Spain.ORCID 0000-0002-0312-5867
Niki ChondrogianniInstitute of Chemical Biology, National Hellenic Research Foundation, 116 35 Athens, Greece.ORCID 0000-0002-5867-0862
Sarmistha SahaDepartment of Biotechnology, Institute of Applied Sciences & Humanities, GLA University, Mathura 00185, Uttar Pradesh, India.ORCID 0000-0001-5324-1957
Alessandra BerryCenter for Behavioral Sciences and Mental Health, Istituto Superiore di Sanità, 00161 Rome, Italy.ORCID 0000-0001-6562-9043
Letizia GionaCenter for Behavioral Sciences and Mental Health, Istituto Superiore di Sanità, 00161 Rome, Italy.ORCID 0009-0008-0093-5080
Joana P MirandaResearch Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisboa, Portugal.ORCID 0000-0002-7804-4068
Elisabetta ProfumoDepartment of Cardiovascular and Endocrine-Metabolic Diseases and Aging, Istituto Superiore di Sanità, 00161 Rome, Italy.ORCID 0000-0002-7261-8884
Sergio DavinelliDepartment of Medicine and Health Sciences "V. Tiberio", University of Molise, 86100 Campobasso, Italy.ORCID 0000-0003-2578-7199
Andreas DaiberDepartment for Cardiology 1, University Medical Center Mainz, Molecular Cardiology, Johannes Gutenberg University, 55131 Mainz, Germany.ORCID 0000-0002-2769-0094
Antonio CuadradoDepartment of Biochemistry, Faculty of Medicine, Autonomous University of Madrid, Centro de Investigación Biomédica en Red Sobre Enfermedades Neurodegenerativas (CIBERNED), National Institute of Health Carlos III (ISCIII), Instituto de Investigación Sanitaria La Paz (IdiPaz), 28049 Madrid, Spain.ORCID 0000-0002-4039-7140
Fabio Di DomenicoDepartment of Biochemical Sciences "A. Rossi Fanelli", Sapienza University, 00185 Rome, Italy.ORCID 0000-0002-2013-209X

Funding

Autonomous Community of Madrid P2022/BMD-7230CIBERNED/ISCIII CB06/05/0010Jerome Lejeune Foundation 2280_2023bSapienza University of Rome RG1181642744DF59Sapienza University of Rome RM11916B78D5711ASapienza University of Rome RM12117A2EC1C9E4Spanish Ministry of Science, Innovation and Universities PDC2021-121421-I00Spanish Ministry of Science, Innovation and Universities PDC2022-133765-I00Spanish Ministry of Science, Innovation and Universities PID2019-110061RB-I00Spanish Ministry of Science, Innovation and Universities PID-2021-122766OB-100
6 · The paper itself

Abstract

Nuclear factor erythroid 2-related factor 2 (NRF2) is a master regulator of cellular homeostasis, overseeing the expression of a wide array of genes involved in cytoprotective processes such as antioxidant and proteostasis control, mitochondrial function, inflammation, and the metabolism of lipids and glucose. The accumulation of misfolded proteins triggers the release, stabilization, and nuclear translocation of NRF2, which in turn enhances the expression of critical components of both the proteasomal and lysosomal degradation pathways. This process facilitates the clearance of toxic protein aggregates, thereby actively maintaining cellular proteostasis. As we age, the efficiency of the NRF2 pathway declines due to several factors including increased activity of its repressors, impaired NRF2-mediated antioxidant and cytoprotective gene expression, and potential epigenetic changes, though the precise mechanisms remain unclear. This leads to diminished antioxidant defenses, increased oxidative damage, and exacerbated metabolic dysregulation and inflammation-key contributors to age-related diseases. Given NRF2's role in mitigating proteotoxic stress, the pharmacological modulation of NRF2 has emerged as a promising therapeutic strategy, even in aged preclinical models. By inducing NRF2, it is possible to mitigate the damaging effects of oxidative stress, metabolic dysfunction, and inflammation, thus reducing protein misfolding. The review highlights NRF2's therapeutic implications for neurodegenerative diseases and cardiovascular conditions, emphasizing its role in improving proteostasis and redox homeostasis Additionally, it summarizes current research into NRF2 as a therapeutic target, offering hope for innovative treatments to counteract the effects of aging and associated diseases.

Indexed as

AgingNF-E2-Related Factor 2ProteostasisAnimalsAntioxidantsHumansOxidation-ReductionOxidative StressAntioxidantsNFE2L2 protein, humanNF-E2-Related Factor 2agingneurodegenerationNRF2oxidative stressproteostasisredox balance

Identifiers

PMID39858508
PMCPMC11764413

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.