Absence of immune stimuli
Immune stimuli
NLRP3
CNS-penetrant NLRP3 inhibitor
Targeting metabolic diseases and neuroinflammation
A key mediator of chronic inflammation that develops with age
NLRP3 is a critical component of the inflammasome, a protein complex that assembles in response to infection and tissue damage and results in inflammation needed to promote healing. However, chronic inflammasome activation leads to pathologic inflammation that drives a vast number of immunologic and fibrotic disorders.
Analysis of BioAge’s proprietary longitudinal human aging cohorts revealed that NLRP3 levels rise with age and are associated with all-cause mortality.
BioAge has discovered a family of chemically novel NLRP3 inhibitors. We have advanced compounds that are both potent and highly brain penetrant, with potential to address a range of metabolic and neuroinflammatory conditions.
Our NLRP3 inhibitors have the potential to corrects
chronic inflammasome activation that is associated
with aging and drives a broad range of diseases
Our NLRP3 inhibitors have the potential
to corrects chronic inflammasome
activation that is associated with aging and drives a broad range of diseases
Our NLRP3 inhibitors have
the potential to corrects chronic
inflammasome activation that is
associated with aging and drives a broad range of diseases
Our NLRP3 inhibitors have the potential to corrects
chronic inflammasome activation that is associated
with aging and drives a broad range of diseases
Our NLRP3 inhibitors have the potential
to corrects chronic inflammasome
activation that is associated with aging and drives a broad range of diseases
Our NLRP3 inhibitors have
the potential to corrects chronic
inflammasome activation that is
associated with aging and drives a broad range of diseases
Young
Inactive NLRP3
NLRP3 inflammasome assembly and activation
Acute cytokine release:
(IL-1β, IL-18)
Acute inflammation to enable immune response to pathogen
Old
Overactive NLRP3 inflammasome
Immune system priming:
↑ NLRP3, ASC, pro-caspase
-
NLRP3
-
ASC
-
Pro-caspase-1
Exaggerated proinflammatory signals:
Cytokine release (IL-1β, IL-18) and pyroptosis (DAMPs)
NLRP3
Prolonged inflammation, even in the absence of pathogen
Acute cytokine release:
(IL-1β, IL-18)
Acute inflammation to enable immune response to pathogen
Exaggerated proinflammatory signals:
Cytokine release (IL-1β, IL-18) and pyroptosis (DAMPs)
NLRP3
Prolonged inflammation, even in the absence of pathogen
BioAge collaborator spotlight
Chronic activation of the NLRP3 inflammasome is associated with aging and is a major contributor to the pathologic inflammation that drives or exacerbates multiple metabolic, immunologic, and fibrotic disorders, as well as neurodegenerative conditions such as Parkinson’s and Alzheimer’s. Inhibition of NLRP3 using small-molecules thus has the potential to treat a broad spectrum
of age-related diseases.
Rebecca Coll, PhD
Wellcome Wolfson Institute for Experimental Medicine
Queen's University Belfast
