Arginine-specific gingipain B (RgpB) (RgpB)

Arginine-specific gingipain B (RgpB) is a potent cysteine protease secreted by the oral pathogen Porphyromonas gingivalis, playing a critical role in the bacterium's virulence and survival. Unlike its counterpart RgpA, RgpB is typically a single-chain enzyme that lacks the large hemagglutinin-adhesion domains, focusing primarily on the degradation of host proteins, including collagen, cytokines, and complement factors. This proteolysis facilitates tissue destruction in periodontitis and allows the pathogen to evade the host immune response by subverting inflammatory pathways. Beyond oral health, RgpB has gained significant attention as a therapeutic target for Alzheimer's disease due to its identification in the brains of affected patients, where it is thought to contribute to tau protein fragmentation and neurotoxicity. Small molecule inhibitors, such as Atuzaginstat (COR388), have been developed to selectively block the catalytic activity of RgpB to mitigate neuroinflammation and cognitive decline. Research continues to explore the systemic implications of RgpB in other chronic inflammatory conditions like rheumatoid arthritis and cardiovascular disease, positioning it as a key link between oral dysbiosis and systemic pathology.

Other names

Gingipain R2Arginine-specific cysteine proteinase BPorphyromonas gingivalis arginine-specific protease BGingipain R

Small molecule irreversible inhibition of the cysteine protease catalytic site, preventing the cleavage of host proteins and reducing bacterial-induced neurodegeneration and inflammation.