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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\u2019s and Parkinson\u2019s 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\u2019s and Parkinson\u2019s 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.<\/jats:p>","DOI":"10.1007\/s11033-025-10878-5","type":"journal-article","created":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T06:44:48Z","timestamp":1753857888000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Effect of natural compounds on NRF2\/KEAP1 signaling in periodontitis: a potential use to prevent age-related disorders"],"prefix":"10.1007","volume":"52","author":[{"given":"Giovanni","family":"Tossetta","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonia","family":"Fantone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabiola","family":"Olivieri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Mazzucchelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucrezia","family":"Togni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Santarelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Marzioni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Rita","family":"Rippo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,7,30]]},"reference":[{"key":"10878_CR1","doi-asserted-by":"crossref","first-page":"S162","DOI":"10.1111\/jcpe.12946","volume":"45","author":"PN Papapanou","year":"2018","unstructured":"Papapanou PN et al (2018) Periodontitis: consensus report of workgroup 2 of the 2017 world workshop on the classification of periodontal and Peri-Implant diseases and conditions. 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