Evidence map›Paper›PMID 41205411›Full record

ArticleRedox biology2025

N-acetyl-l-cysteine ethyl ester (NACET) induces the transcription factor NRF2 and prevents retinal aging and diabetic retinopathy.

Giulia Realini, Rosario Amato, Mahdi Rasa, Roberto Ceccatelli, Angela Cannavale, Laura Bottoni, Federico Marchini, Alberto Minetti, Daniela Giustarini, Alessio Canovai and 12 more

Abstract read
In one paragraph

Article in Redox biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. The neuroimmune-glutamate hypothesis of addiction.Neuroscience and biobehavioral reviews · 2026
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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

22 authors.

Giulia RealiniDepartment of Biotechnology, Chemistry and Pharmacy, University of Siena, Via Aldo Moro 2, Siena, 53100, Italy.
Rosario AmatoDepartment of Biology, University of Pisa, Pisa, 56127, Italy.
Mahdi RasaLeibniz Institute on Aging - Fritz Lipmann Institute (FLI), Jena, Germany.
Roberto CeccatelliDepartment of Biotechnology, Chemistry and Pharmacy, University of Siena, Via Aldo Moro 2, Siena, 53100, Italy.
Angela CannavaleDepartment of Biology, University of Pisa, Pisa, 56127, Italy.
Laura BottoniDepartment of Biotechnology, Chemistry and Pharmacy, University of Siena, Via Aldo Moro 2, Siena, 53100, Italy.
Federico MarchiniDepartment of Biotechnology, Chemistry and Pharmacy, University of Siena, Via Aldo Moro 2, Siena, 53100, Italy.
Alberto MinettiDepartment of Biotechnology, Chemistry and Pharmacy, University of Siena, Via Aldo Moro 2, Siena, 53100, Italy; Leibniz Institute on Aging - Fritz Lipmann Institute (FLI), Jena, Germany.
Daniela GiustariniDepartment of Biotechnology, Chemistry and Pharmacy, University of Siena, Via Aldo Moro 2, Siena, 53100, Italy.
Alessio CanovaiDepartment of Biology, University of Pisa, Pisa, 56127, Italy.
Alberto MelecchiDepartment of Biology, University of Pisa, Pisa, 56127, Italy.
Ines EliaDepartment of Biotechnology, Chemistry and Pharmacy, University of Siena, Via Aldo Moro 2, Siena, 53100, Italy.
Anna KrepelovaDepartment of Life Sciences and Systems Biology, University of Turin, Torino, Italy.
Francesco AnnunziataLeibniz Institute on Aging - Fritz Lipmann Institute (FLI), Jena, Germany.
Maurizio CammalleriDepartment of Biology, University of Pisa, Pisa, 56127, Italy.
Ranieri RossiDepartment of Biotechnology, Chemistry and Pharmacy, University of Siena, Via Aldo Moro 2, Siena, 53100, Italy.
Gian Marco TosiDepartment of Medicine, Surgery and Neuroscience, University of Siena, Siena, 53100, Italy.
Maurizio OrlandiniDepartment of Biotechnology, Chemistry and Pharmacy, University of Siena, Via Aldo Moro 2, Siena, 53100, Italy.
Mario ChiarielloIstituto di Fisiologia Clinica (IFC), Consiglio Nazionale Delle Ricerche (CNR) and Core Research Laboratory, Istituto per lo Studio, la Prevenzione e la Rete Oncologica (ISPRO), Siena, 53100, Italy.
Francesco NeriLeibniz Institute on Aging - Fritz Lipmann Institute (FLI), Jena, Germany; Department of Life Sciences and Systems Biology, University of Turin, Torino, Italy; Molecular Biotechnology Center, University of Turin, Torino, Italy.
Massimo Dal MonteDepartment of Biology, University of Pisa, Pisa, 56127, Italy.
Federico GalvagniDepartment of Biotechnology, Chemistry and Pharmacy, University of Siena, Via Aldo Moro 2, Siena, 53100, Italy. Electronic address: federico.galvagni@unisi.it.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Age-related macular degeneration (AMD) and diabetic retinopathy (DR) are leading causes of visual impairment in older people, with oxidative stress playing a central role in the development of these diseases. In this study, we showed that N-acetylcysteine ethyl ester (NACET) not only increases intracellular cysteine and glutathione levels, but also strongly stimulates the expression and activity of the transcription factor NRF2, a master regulator of oxidative stress response, in RPE cells. Using RNA interference, mass spectrometry and mutagenesis of the NRF2 regulator KEAP1, we identified direct cysteinylation of the sensor residues Cys226 and Cys613 on KEAP1 as the molecular mechanism underlying NRF2 activation after NACET treatment. Furthermore, we demonstrated that oral administration of NACET induces NRF2 activity in the retina in vivo, attenuates retinal aging hallmarks, and prevents diabetes-induced retinal neurodegeneration in mouse models. These results position NACET as a promising therapeutic candidate for age- and oxidative stress-related retinal diseases such as AMD and DR.

Indexed as

AcetylcysteineDiabetic RetinopathyNF-E2-Related Factor 2RetinaAgingAnimalsDisease Models, AnimalHumansKelch-Like ECH-Associated Protein 1Macular DegenerationMiceOxidative StressRetinal Pigment EpitheliumAcetylcysteineKelch-Like ECH-Associated Protein 1NFE2L2 protein, humanNF-E2-Related Factor 2Age-related macular degeneration (AMD)Cysteine (Cys)Cystine (Cyss)Diabetic retinopathy (DR)Kelch-like ECH-Associated protein 1 (KEAP1)N-Acetylcysteine ethyl ester (NACET)NF-E2-related factor 2 (NRF2)Oxidative stress

Identifiers

PMID41205411
PMCPMC12793733

What Socratic holds

Textmetadata
LicenceCC BY
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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 Socratic graph.