NLRP3 inflammasome: a new target in major depressive disorder.

Inflammasome has emerged recently as an unexpected sensor for metabolic danger and stress. Indeed, it has been implicated in the development of major diseases such as gout, type 2 diabetes, and obesity-induced insulin resistance and is increasingly suspected of playing a major role in other human pathologies such as cancer, asbestosis, and Alzheimer’s disease. The inflammasome is a protein complex that comprises an intracellular sensor, typically a Nod-like receptor (NLR), the precursor procaspase-1, and the adaptor ASC. Inflammasome activation leads to the maturation of caspase-1 and the processing of its substrates, IL-1b, and IL-18. Of all the NLRs, NLRP3 is activated by the most diverse array of danger signals. Recently, it has been hypothesized the implication of inflammasome in depression and related comorbid systemic illnesses, however, was necessary to demonstrate the activation of NLRP3 inflammasome in depressive patients. This event was intuited because IL-1b, one of the two known cytokines activated by the inflammasome complex, has been implicated in stress, depression, and central nervous system (CNS) dysregulation. A recent paper published in CNS Neuroscience and Therapeutics by Zhang et al. have showed in first time that the NLRP3 inflammasome is involved in lipopolysaccharideinduced mice depressive-like behaviors. In parallel, the authors of the present paper have showed in first time the activation of NLRP3 inflammasome in blood mononuclear cells from depressive patients with a high correlation between IL1b and IL-18 with Beck Depression Inventory scores of depressive patients. These are two papers demonstrating in an animal model and patients, the hypothesis of Iwata et al. These findings provide new insight into the pathogenesis of major depressive disorder. Now, we must deepen about this and study several point involved in the pathogenesis of this disease.