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Immunol."],"abstract":"<jats:p><jats:italic>Porphyromonas gingivalis<\/jats:italic> (<jats:italic>P. gingivalis<\/jats:italic>) is a gram-negative bacterium and the main causative agent of periodontitis, a disease closely associated with the development of periodontal disease. The progression of periodontitis, a chronic infectious disease, is intricately linked to the inflammatory immune response. Inflammatory cytokines act on periodontal tissues via immunomodulation, resulting in the destruction of the periodontal tissue. Recent studies have established connections between periodontitis and various systemic diseases, including cardiovascular diseases, tumors, and neurodegenerative diseases. Neurodegenerative diseases are neurological disorders caused by immune system dysfunction, including Alzheimer\u2019s and Parkinson\u2019s diseases. One of the main characteristics of neurodegenerative diseases is an impaired inflammatory response, which mediates neuroinflammation through microglial activation. Some studies have shown an association between periodontitis and neurodegenerative diseases, with <jats:italic>P. gingivalis<\/jats:italic> as the primary culprit. <jats:italic>P. gingivalis<\/jats:italic> can cross the blood-brain barrier (BBB) or mediate neuroinflammation and injury through a variety of pathways, including the gut-brain axis, thereby affecting neuronal growth and survival and participating in the onset and progression of neurodegenerative diseases. However, comprehensive and systematic summaries of studies on the infectious origin of neurodegenerative diseases are lacking. This article reviews and summarizes the relationship between <jats:italic>P. gingivalis<\/jats:italic> and neurodegenerative diseases and its possible regulatory mechanisms. This review offers new perspectives into the understanding of neurodegenerative disease development and highlights innovative approaches for investigating and developing tailored medications for treating neurodegenerative conditions, particularly from the viewpoint of their association with <jats:italic>P. gingivalis<\/jats:italic>.<\/jats:p>","DOI":"10.3389\/fimmu.2025.1482033","type":"journal-article","created":{"date-parts":[[2025,2,14]],"date-time":"2025-02-14T05:10:45Z","timestamp":1739509845000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":42,"title":["Porphyromonas gingivalis: a potential trigger of neurodegenerative disease"],"prefix":"10.3389","volume":"16","author":[{"given":"Ziyan","family":"Huang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miao","family":"Hao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naixu","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyu","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haotian","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofeng","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,2,14]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1902\/jop.2015.140520","article-title":"Update on prevalence of periodontitis in adults in the United States: NHANES 2009 to 2012","volume":"86","author":"Eke","year":"2015","journal-title":"J Periodontol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2016.00053","article-title":"Porphyromonas gingivalis: an overview of periodontopathic pathogen below the gum line","volume":"7","author":"How","year":"2016","journal-title":"Front Microbiol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0765.2008.01131.x","article-title":"Elevation of C-reactive protein and interleukin-6 in plasma of patients with aggressive periodontitis","volume":"44","author":"Sun","year":"2009","journal-title":"J\u00a0Periodontal Res"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinthera.2019.02.001","article-title":"Chronic low-grade inflammatory phenotype (CLIP) and senescent immune dysregulation","volume":"41","author":"Chen","year":"2019","journal-title":"Clin Ther"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2000.tb06651.x","article-title":"Inflamm-aging. 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