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Altered NRF2 signalling in systemic redox imbalance: Insights from non-communicable diseases

Monika Jakubowska1, Vera Marisa Costa2, Wojciech Krzeptowski3

  • 1Malopolska Centre of Biotechnology, Jagiellonian University in Krakow, Krakow, Poland.

Redox Biology
|October 18, 2025
PubMed

Insights

Assessing Nuclear factor erythroid 2-related factor 2 (NRF2) activity in blood samples offers insights into its role in various diseases. This approach aids in understanding NRF2

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cellular Biology

Background:

  • Nuclear factor erythroid 2-related factor 2 (NRF2) is a key transcription factor regulating cellular defense mechanisms.
  • Balanced NRF2 activity is crucial for maintaining homeostasis and combating pathologies, including non-communicable diseases (NCDs).
  • Systemic detection of NRF2 activity products may reflect local tissue responses, necessitating accessible measurement methods.

Purpose of the Study:

  • To evaluate the clinical utility of a panel of six NRF2 activity biomarkers in accessible human samples.
  • To assess the connection between NRF2 activation and the diagnosis, progression, and therapeutic response in NCDs.

Main Methods:

  • Utilized a previously identified panel of six biomarkers: Glutamate-cysteine ligase catalytic subunit (GCLC), Glutamate-cysteine ligase modifier subunit (GCLM), Haem oxygenase 1 (HMOX1), NAD(P)H quinone dehydrogenase 1 (NQO1), Sulfiredoxin 1 (SRXN1), and Thioredoxin reductase 1 (TXNRD1).
  • Assessed the biomarkers' utility in a clinical setting to measure NRF2 activation in disease contexts.
  • Discussed findings on how NRF2 activity in blood and biofluids can reveal its involvement in NCDs.

Main Results:

  • The study validated the utility of the six biomarkers for measuring NRF2 activity in clinical samples.
  • NRF2 activity in accessible samples correlates with various NCDs, offering insights into disease mechanisms.
  • Findings suggest NRF2 activity is linked to clinical aspects like diagnosis, disease progression, and treatment response.

Conclusions:

  • Measuring NRF2 activity in accessible human samples provides a valuable tool for clinical assessment of NCDs.
  • This approach can help infer NRF2 responses in local tissues and inform clinical management.
  • The identified biomarkers serve as indicators of NRF2 activation relevant to disease states.
Keywords:
BiomarkerNRF2Non-communicable diseasesOxidative stressRedox imbalanceTranscription factor

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