This technology utilizes a C-terminal peptide consisting of amino acids 195–288 of the Toxoplasma gondii secretory protein GRA9, or the gene encoding it, as an active ingredient. It is designed for pharmaceutical and health functional food compositions to prevent and treat Parkinson's disease, Alzheimer's disease, inflammatory bowel disease, atherosclerosis, and sepsis. This peptide blocks the NLRP3 inflammasome, the trigger for excessive inflammatory responses in macrophages.
The NLRP3 inflammasome is linked to various degenerative and chronic inflammatory diseases by maturing IL-1β and IL-18 and inducing pyroptosis, an inflammatory form of cell death. Furthermore, the hyperinflammatory response in early-stage sepsis has been a primary cause of high mortality. However, while Toxoplasma gondii GRA9 had been proposed as a vaccine candidate, its role in modulating the host immune system—specifically its relationship with the NLRP3 inflammasome—remained largely unknown.
This technology identifies that the glutamine at position 200 of the GRA9 C-terminus is essential for its function. The peptide directly binds to NLRP3 in macrophage mitochondria to inhibit inflammasome formation while promoting M2 macrophage polarization and phagocytosis, providing both anti-inflammatory and antibacterial effects. Applicable to peptide-based sepsis treatments, therapies for NLRP3-related neurodegenerative diseases, and inflammatory bowel disease supplements, it leverages a protein fragment evolved by the parasite to evade host immunity, achieving the dual effect of suppressing inflammation while enhancing bacterial clearance.
This invention was developed with support from the Ministry of Education for the analysis of host immune modulation mechanisms based on Toxoplasma gondii antigens and their therapeutic applications.
US11939360B2
