Effect of natural compounds on NRF2/KEAP1 signaling in periodontitis: a potential use to prevent age-related disorders

40% of the population over 60 years of age is affected by periodontitis which is characterized by chronic inflammation, periodontal damage and alveolar bone resorption. The nuclear factor erythroid 2-related factor 2 (NFE2L2 or NRF2)/ Kelch-like ECH-Associated Protein 1 (KEAP1) (NRF2/KEAP1) signaling pathway plays a key role in periodontitis modulating redox balance and periodontium inflammation. However, NRF2 expression decreases in gingival tissues of severe periodontitis patients while Reactive Oxygen Species (ROS) levels are increased during periodontitis. ROS and lipopolysaccharide (LPS) produced by gram-negative bacteria favor the production of inflammatory cytokines, then causing periodontal inflammation and favoring alveolar bone loss (due to excessive osteoclast formation and activation). Periodontitis has also been associated to the development of age-related neurodegenerative diseases such as Alzheimer’s and Parkinson’s diseases since the increased cytokines levels and the bacteria themselves present in the periodontium can easily reach the brain due to their anatomical proximity. Thus, periodontitis could be considered a risk factor for the development of Alzheimer’s and Parkinson’s diseases. In this review we explored the role of NRF2/KEAP1 signaling activation in in vitro and in vivo models of periodontitis to suggest potential treatments of periodontitis and avoid/delay the development of age-related neurodegenerative diseases.

• Publication year

  2025

• Venue

  Molecular Biology Reports

• Publication date

  2025-07-30

• Fields of study

  Medicine, Environmental Science

• Identifiers
  DOI 10.1007/s11033-025-10878-5PMID 40736688PMCID 12310809
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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