Importance of the inflammasome in gut-brain axis: from pathological driver to therapeutic target.
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The inflammasome, a supramolecular complex, plays important role in the gut-brain axis (GBA), acting as a sensor of cellular stress and danger signals. It activates inflammatory responses, and its dysregulation has been implicated in neurological diseases. Various inflammasomes, such as NLRP3, NLRC4, and AIM2, contribute to disease progression by promoting inflammation, tissue damage, and oxidative stress. These inflammasomes recognize and get activated by different stimuli, such as ATP, fluctuations in ion fluxes, nucleic acids, and molecular signatures associated with pathogens, eventually releasing inflammatory cytokines, and triggering inflammatory responses. Although the inflammatory response is orchestrated, sometimes it might happen that its dysregulation causes excessive and sustained inflammation leading to cellular damage and tissue injuries. Inhibiting or modulating these inflammasomes can therefore, provide therapeutic benefits. Targeting NLRP3, like MCC950, has shown promise in reducing inflammation. Some natural compounds have also been found to inhibit NLRP3 and other inflammasomes. Interestingly, regulating the gut microbiome can impact inflammasome activation, and reduce unsolicited inflammation. This review explores the bidirectional communication network between the gut and brain, and emphasizes the importance of understanding the role of inflammasomes in the GBA which can lead to novel therapeutic strategies for neurological diseases like Multiple Sclerosis, Parkinson's, and Alzheimer's.