Moving upstream – from single-cytokine blockade to NLRP3-driven inflammation control
Inflammation is a crucial biological response that protects us against tissue damage and/or infection – yet it can also become persistent and exaggerated in the absence of these events, driving the development and progression of cardiometabolic and neuroinflammatory diseases.
Pro-inflammatory cytokines such as IL-1β, IL-18 and IL-6 play a key role in this disease-causing inflammation and have been extensively explored (IL-1β blockers) or are being actively explored (IL-6 blockers, IL-18 blockers) as therapeutic targets. However, biologics that block IL-1β, IL-18 and IL-6 have notable limitations: they require injectable administration and involve complex and high-cost manufacturing, and anti-IL-1β therapies have been associated with an increased risk of infection.
NLRP3 sits upstream of IL-1β and IL-18, acting as a key intracellular sensor of metabolic and aging- related danger signals that trigger NLRP3–IL-1β/IL-18 inflammatory cascades with downstream effects on IL-6 and CRP. As a central regulator of inflammation that can be selectively targeted with oral small molecules, NLRP3 represents a promising therapeutic target for cardiometabolic and neuroinflammatory diseases, with the potential to reduce disease-causing inflammation while preserving host defense, through convenient and cost-effective oral dosing.
Pro-inflammatory cytokines such as IL-1β, IL-18 and IL-6 play a key role in this disease-causing inflammation and have been extensively explored (IL-1β blockers) or are being actively explored (IL-6 blockers, IL-18 blockers) as therapeutic targets. However, biologics that block IL-1β, IL-18 and IL-6 have notable limitations: they require injectable administration and involve complex and high-cost manufacturing, and anti-IL-1β therapies have been associated with an increased risk of infection.
NLRP3 sits upstream of IL-1β and IL-18, acting as a key intracellular sensor of metabolic and aging- related danger signals that trigger NLRP3–IL-1β/IL-18 inflammatory cascades with downstream effects on IL-6 and CRP. As a central regulator of inflammation that can be selectively targeted with oral small molecules, NLRP3 represents a promising therapeutic target for cardiometabolic and neuroinflammatory diseases, with the potential to reduce disease-causing inflammation while preserving host defense, through convenient and cost-effective oral dosing.
NLRP3 inflammasome assembly
