Pathological implications of Porphyromonas gingivalis in Alzheimer’s disease and therapeutic potential of gingipain inhibitors
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Porphyromonas gingivalis is a key pathogen in periodontitis associated with Alzheimer’s disease (AD) through multiple mechanisms. Recent findings regarding the existence of its DNA and proteins in AD’s brain tissues reveal its ability to breach the blood–brain barrier (BBB). This study overviews the potential mechanisms of action of P. gingivalis , including its direct migration to the brain via BBB disruption and indirect effects mediated by outer membrane vesicles carrying toxic components, such as gingipains, lipopolysaccharides, and fimbriae. The implications of P. gingivalis-induced neuroinflammation, amyloid-β aggregation, and tubulinassociated unit protein modification in AD pathology, together with emerging therapeutic strategies targeting gingipain, were also explored.
Abstract
Porphyromonas gingivalis is a key pathogen in periodontitis associated with Alzheimer’s disease (AD) through multiple mechanisms. Recent findings regarding the existence of its DNA and proteins in AD’s brain tissues reveal its ability to breach the blood–brain barrier (BBB). This study overviews the potential mechanisms of action of P. gingivalis , including its direct migration to the brain via BBB disruption and indirect effects mediated by outer membrane vesicles carrying toxic components, such as gingipains, lipopolysaccharides, and fimbriae. The implications of P. gingivalis-induced neuroinflammation, amyloid-β aggregation, and tubulinassociated unit protein modification in AD pathology, together with emerging therapeutic strategies targeting gingipain, were also explored.