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An Overview of the Nrf2/ARE Pathway and Its Role in Neurodegenerative Diseases

Emilia Zgorzynska1, Barbara Dziedzic1, Anna Walczewska1

  • 1Department of Cell-to-Cell Communication, Medical University of Lodz, Mazowiecka 6/8, 92-215 Lodz, Poland.

International Journal of Molecular Sciences
|September 10, 2021
PubMed

Insights

The Nrf2-ARE pathway is crucial for cellular defense against oxidative stress. Dysregulation of this pathway contributes to neurodegenerative diseases, but molecules targeting Nrf2 show therapeutic potential.

Area of Science:

  • Molecular Biology
  • Neuroscience
  • Biochemistry

Background:

  • Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor regulating antioxidant and detoxification genes.
  • Nrf2 is typically sequestered by Kelch-like ECH-associated protein 1 (Keap1), targeting it for degradation.
  • Oxidative stress, neuroinflammation, and mitochondrial dysfunction are key features of neurodegenerative diseases.

Purpose of the Study:

  • To review the role of Nrf2-ARE pathway dysfunctions in neurodegenerative diseases.
  • To explore the therapeutic potential of molecules targeting the Nrf2 pathway for neuroprotection.

Main Methods:

  • Literature review of studies investigating Nrf2/ARE signaling in neurological pathologies.
  • Analysis of evidence linking pathway dysfunction to Alzheimer's, Parkinson's, Huntington's diseases, and ALS.
  • Examination of natural and synthetic compounds modulating Nrf2 activity.

Main Results:

  • Evidence indicates Nrf2/ARE pathway dysregulation is implicated in the pathogenesis of major neurodegenerative diseases.
  • Activation of Nrf2 enhances the expression of protective genes, counteracting cellular damage.
  • Various molecules demonstrate the ability to interact with Nrf2, boosting its protective functions.

Conclusions:

  • Targeting the Nrf2-ARE pathway offers a promising strategy for preventing or delaying neurodegenerative diseases.
  • Further research into Nrf2-activating compounds could lead to novel therapeutic interventions for neurological disorders.
Keywords:
Alzheimer’s diseaseHuntington’s diseaseKeap1Nrf2Parkinson’s diseaseamyotrophic lateral sclerosisneurodegenerative diseasesneuroprotectionoxidative stress

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