Microglia is a kind of resident immune cell in the central nervous system (CNS) parenchyma. microglia remain in a quiescent state Under normal physiological conditions. Besides, Brain injury and some psychophysiological conditions lead to microglia activation.
NLRP3 plays an important role in the regulation of microglia-induced inflammation. Besides, The improved NLRP3 expression is highly related to the pathogenesis of brain injury and CNS diseases. Activated-NLRP3 stimulates caspase-1′s activity. As a result, it leads to the maturation and subsequent release of pro-inflammatory cytokine IL-1β. IL-1β increased the expression of iNOS in microglia. Subsequently, microglia activation may lead to acute and chronic disorders including brain trauma, sepsis, ischemic stroke, schizophrenia, etc.
The inhibition of the microglia-mediated inflammation is a promising approach for neuro-inflammatory disease research. AMS-17 is an Isoliquiritigenin derivative.
AMS-17 is a potent NLRP3 inflammasome inhibitor.
It does not affect the viability of N9 cells. However, it inhibits NLRP3 and iNOS expression induced by LPS in a dose-dependent manner.
Phagocytosis plays an important role in the microglial clearance of apoptotic cell debris. In N9 cells, LPS increases the phagocytosis of microglia. However, AMS-17 reduces the cellular uptake of fluorescence intensity of Aβ42. AMS-17 maintains microglia morphology in the resting state. quiescent N9 cells are elongated, bipolar, and rod-shaped. But LPS stimulation leads to 18% of cells in a resting state. AMS-17 is able to suppress microglial activation in vitro. The percentage of AMS-17 reaches 65%.
In conclusion, AMS-17 inhibits inflammatory responses in microglia by inhibiting the NLRP3 pathway. And it also suppresses microglia activation induced by LPS. AMS-17 is a potent brain penetration inhibitor and can be used for inflammation-associated neurological disorders research.