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The Anti-Inflammatory and Anti-Oxidant Mechanisms of the Keap1/Nrf2/ARE Signaling Pathway in Chronic Diseases

Wenjun Tu1,2,3, Hong Wang4, Song Li1

  • 11Institute of Radiation Medicine, China Academy of Medical Science & Peking Union Medical College, Tianjin, China.

Aging and Disease
|June 6, 2019
PubMed

Insights

Oxidative stress, an imbalance in antioxidants, damages cells. The Keap1/Nrf2/ARE pathway is crucial for cellular defense and a potential therapeutic target for various diseases.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cellular Biology

Background:

  • Oxidative stress arises from an imbalance between reactive oxygen species (ROS) production and antioxidant defenses, leading to cellular and biomolecular damage.
  • The Kelch-like ECH-associated protein 1 (Keap1)-nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant response elements (ARE) pathway is central to cellular defense against oxidative stress.
  • This pathway regulates antioxidant and detoxification genes, maintaining cellular homeostasis and protecting against damage from toxins and carcinogens.

Purpose of the Study:

  • To review and discuss recent advancements in the regulation of the Keap1/Nrf2/ARE system.
  • To explore the role of the Keap1/Nrf2/ARE pathway in various physiological and pathophysiological conditions.
  • To highlight the Keap1/Nrf2/ARE pathway as a potential pharmacological target.

Main Methods:

  • Literature review of recent advancements in Keap1/Nrf2/ARE pathway research.
  • Analysis of the pathway's function in physiological states (e.g., exercise).
  • Examination of the pathway's involvement in pathophysiological conditions (e.g., diabetes, cardiovascular diseases, cancer, neurodegenerative disorders, stroke, liver and kidney diseases).

Main Results:

  • The Keap1/Nrf2/ARE pathway is a critical redox-sensitive signaling system for maintaining cellular homeostasis under stress.
  • Dysregulation of this pathway is implicated in numerous diseases, including cancer, neurodegenerative disorders, and metabolic diseases.
  • The pathway's role in cellular defense and detoxification makes it a promising target for therapeutic intervention.

Conclusions:

  • The Keap1/Nrf2/ARE pathway is a key regulator of cellular response to oxidative stress and plays a significant role in health and disease.
  • Understanding the intricate regulation of this pathway provides insights into disease mechanisms and potential treatment strategies.
  • Targeting the Keap1/Nrf2/ARE system offers a promising avenue for developing novel therapies for a wide range of oxidative stress-related disorders.
Keywords:
Anti-inflammatoryAnti-oxidantKeap1/Nrf2/ARELow-level laser irradiationOxidative stressReactive oxygen species

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