NLRP3-Dependent Pyroptosis: A Candidate Therapeutic Target for Depression

Abstract

Depression, a major public health problem, imposes a significant economic burden on society. Recent studies have gradually unveiled the important role of neuroinflammation in the pathogenesis of depression. Pyroptosis, a programmed cell death mediated by Gasdermins (GSDMs), is also considered to be an inflammatory cell death with links to inflammation. Pyroptosis has emerged as an important pathological mechanism in several neurological diseases and has been found to be involved in several neuroinflammatory-related diseases. A variety of chemical agents and natural products have been found to be capable of exerting therapeutic effects by modulating pyroptosis. Studies have shown that depression is closely associated with pyroptosis and the induced neuroinflammation of relevant brain regions, such as the hippocampus, amygdala, prefrontal cortex neurons, etc., in which the nucleotide-binding oligomerization domain-like receptor protein 3 inflammasome plays a crucial role. This article provides a timely review of recent findings on the activation and regulation of pyroptosis in relation to depression.

Ferroptosis, Necroptosis, and Pyroptosis in Gastrointestinal Cancers: The Chief Culprits of Tumor Progression and Drug Resistance

“…Additionally, caspase-1 promotes the secretion of interleukins, leading to an inflammatory response. [48][49][50][51][52][53] The nonclassical pathway of pyroptosis is mediated primarily by caspase-4, 5, and 11. Activation of these caspases occurs upon stimulation of cells with bacterial LPS, whereby they bind directly to LPS and subsequently become activated.…”

“…Additionally, caspase‐1 promotes the secretion of interleukins, leading to an inflammatory response. [ 48–53 ]…”

Role of NLRP3 Inflammasome in Post-Spinal-Cord-Injury Anxiety and Depression: Molecular Mechanisms and Therapeutic Implications

“…The NLRP3 inflammasome and subsequent pyroptosis have emerged as potential therapeutic targets for the treatment of depression . Several agents have shown promise in modulating the NLRP3 inflammasome and exerting antidepressant effects.…”

“…The NLRP3 inflammasome and subsequent pyroptosis have emerged as potential therapeutic targets for the treatment of depression. 163 Several agents have shown promise in modulating the NLRP3 inflammasome and exerting antidepressant effects. For example, a Food and Drug Administration (FDA)-approved antidepressant, fluoxetine, was found to bind NLRP3 in silico and inhibit the NLRP3-ASC complex in vitro and in vivo.…”

Biology of cyclooxygenase-2: An application in depression therapeutics

“…In recent years, an increasing number of scholars have found that neuroinflammation is an important pathological factor triggering central neurological disorders such as depression, and inhibiting central neuroinflammation is a key way to effectively alleviate the onset and progression of depression (12)(13)(14)(15)(16). It was found that upregulation of pro-inflammatory cytokines (IL-6 and TNF-α) was seen in the hippocampus and cortex of Lipopolysaccharide (LSP)-induced depressed mice (17).…”