Arginine-specific gingipain (Rgp) (Rgp)

Arginine-specific gingipain (Rgp) is a critical cysteine protease and virulence factor secreted by Porphyromonas gingivalis, a key pathogen in chronic periodontitis [1, 5]. These enzymes, produced as the gene products RgpA and RgpB, specifically cleave proteins at the C-terminus of arginine residues, facilitating bacterial survival and host tissue destruction [1, 3, 8]. Rgp plays essential roles in the degradation of extracellular matrix components, the inactivation of host immune factors such as cytokines and complement proteins, and the acquisition of iron via hemoglobin breakdown [1, 7, 9]. Beyond oral pathology, Rgp has been strongly implicated in the pathogenesis of Alzheimer's disease, with evidence showing that these proteases can traverse to the brain and promote tau protein fragmentation and neuroinflammation [6]. Consequently, Rgp serves as a therapeutic target for small-molecule inhibitors designed to slow the progression of periodontitis and associated systemic diseases [4, 6]. While clinical candidates like atuzaginstat (COR388) have been developed to target this enzyme, their clinical application has been challenged by safety concerns such as liver toxicity [6].

Other names

Gingipain RR-gingipainArginine-specific cysteine proteinaseRgpARgpBArg-gingipainArginine-specific cysteine protease

Small-molecule irreversible inhibition of the arginine-specific gingipain catalytic domain, which prevents the cleavage of host proteins such as Tau and cytokines, thereby disrupting bacterial nutrient acquisition and reducing neurotoxicity and inflammatory damage.