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The role of Nrf2 signaling in counteracting neurodegenerative diseases

Albena T Dinkova-Kostova1,2, Rumen V Kostov1, Aleksey G Kazantsev3

  • 1Division of Cancer Research, School of Medicine, University of Dundee, UK.

The FEBS Journal
|January 12, 2018
PubMed

Insights

The transcription factor Nrf2 (nuclear factor-erythroid 2 p45-related factor 2) plays a key role in cellular defense and metabolism. Activating Nrf2 shows therapeutic potential for neurodegenerative diseases by mitigating pathogenic processes.

Area of Science:

  • Cellular Biology
  • Neuroscience
  • Metabolism

Background:

  • Nuclear factor-erythroid 2 p45-related factor 2 (Nrf2) is a transcription factor crucial for cellular redox balance and metabolism.
  • Nrf2 regulates genes involved in antioxidant defense, detoxification, protein/organelle repair, inflammation, and mitochondrial function.
  • Altered Nrf2 function is implicated in neurodegenerative disorders like Alzheimer's, Parkinson's, ALS, and Huntington's disease.

Purpose of the Study:

  • To investigate the role of Nrf2 in neurodegenerative disease pathogenesis.
  • To evaluate the therapeutic potential of Nrf2 activation in neurodegenerative disorders.

Main Methods:

  • Review of literature on Nrf2 function and its involvement in neurodegeneration.
  • Analysis of studies using small molecule activators of Nrf2 in cellular and animal models.

Main Results:

  • Nrf2 activation effectively mitigates key pathogenic processes in neurodegenerative diseases.
  • Upregulation of antioxidant defenses, reduced inflammation, improved mitochondrial function, and maintained protein homeostasis are observed.
  • Pharmacological Nrf2 activators demonstrate protective effects in various neurodegenerative disease models.

Conclusions:

  • Targeting Nrf2 signaling represents a promising therapeutic strategy for neurodegenerative disorders.
  • Nrf2 activation may delay disease onset, slow progression, and alleviate symptoms.
  • Further research into Nrf2-based therapies is warranted for conditions like Alzheimer's and Parkinson's disease.
Keywords:
Nrf2 activatorneurodegenerationneuroinflammationneuroprotectionoxidative stress

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