Impact of brain dysfunction by Porphyromonas gingivalis and neutrophil extracellular traps in periodontal disease

Abstract

Gingipains, cysteine proteases produced by the periodontopathic bacterium Porphyromonas gingivalis, not only exacerbate periodontal disease but have also been implicated in the pathogenesis of Alzheimer’s disease （AD）, rheumatoid arthritis or diabetes mellitus. Neutrophil extracellular traps （NETs） released by oral neutrophils contribute to the maintenance of oral homeostasis, whereas NETs released upon stimulation by periodontopathic bacteria exacerbate inflammatory responses. This review outlines the impact of periodontal disease on the pathogenesis of brain dysfunction, including AD, focusing on gingipains and NETs. Gingipains have been implicated in the induction of chronic inflammation in periodontal disease. Gingipains have also been implicated in the pathogenesis of AD, and clinical trials of gingipain inhibitors have shown improved rates of cognitive decline in periodontal patients with P. gingivalis infection. Oral neutrophils play a role in infection defense by continuously releasing NETs upon stimulation by oral flora and saliva. However, NETs released by oral neutrophils upon stimulation by periodontopathic bacteria have lost their ability to protect against infection and induce inflammation.