NLRP3 inflammasome in ischemic stroke: As possible therapeutic target

Abstract

Inflammation is a devastating pathophysiological process during stroke, a devastating disease that is the second most common cause of death worldwide. Activation of the NOD-like receptor protein (NLRP3)-infammasome has been proposed to mediate inflammatory responses during ischemic stroke. Briefly, NLRP3 inflammasome activates caspase-1, which cleaves both pro-IL-1 and pro-IL-18 into their active pro-inflammatory cytokines that are released into the extracellular environment. Several NLRP3 inflammasome inhibitors have been promoted, including small molecules, type I interferon, micro RNAs, nitric oxide, and nuclear factor erythroid-2 related factor 2 (Nrf2), some of which are potentially efficacious clinically. This review will describe the structure and cellular signaling pathways of the NLRP3 inflammasome during ischemic stroke, and current evidence for NLRP3 inflammasome inhibitors.

Meisoindigo Protects Against Focal Cerebral Ischemia-Reperfusion Injury by Inhibiting NLRP3 Inflammasome Activation and Regulating Microglia/Macrophage Polarization via TLR4/NF-κB Signaling Pathway

“…One possible mechanism may be that meisoindigo inhibits NLRP3 inflammasome activation both in neurons and microglia/macrophages. When the NLRP3 inflammasome of neurons is inactivated by meisoindigo, neuronal pyroptosis is reduced (Alishahi et al, 2019), and the pro-inflammatory cytokines such as IL-18, IL-1β and IL-6 are unreleased, then the exogenous stimulant derived from neurons on infiltration, activation and polarization of microglia/macrophage is decreased. In addition, meisoindigo at the same time inhibits NLRP3 inflammasome activation of microglia/macrophage themselves, also blocks their endogenous initiate of infiltration, activation and polarization.…”

Neuroprotective Effects of Qingnao Dripping Pills Against Cerebral Ischemia via Inhibiting NLRP3 Inflammasome Signaling Pathway: In Vivo and In Vitro

“…The studies reported that the activation of the NLRP3 inflammasome leads to the development and release of inflammatory cytokines IL-1b and IL-18, suggesting the role for the NLRP3 inflammasome in the initiation and development of cerebral ischemia (Rathinam et al, 2012;Gao et al, 2017). Accumulating amounts of evidence have indicated that NLRP3 inflammasome activation was closely related with postischemic inflammation after stroke, which was critical in neuronal cell death in ischemic stroke (Zhang et al, 2017;Alishahi et al, 2019).…”

Neurovascular Inflammaging in Health and Disease

“…All these stimuli facilitate production and secretion of IL-1β and IL-18, ultimately leading to further neuronal and glial death in the ischemic and hemorrhagic tissue, and contributing to exacerbation of neurological deficits [139,145,146]. Even though majority of the studies are centered around the NLRP3 inflammasome and its role in stroke pathophysiology [138,147], multiple other inflammasome constituents have been addressed in inflammatory responses of the NVU related to stroke. These are NLRP1 [139,148], NLRP2 [149,150], NLRP6 [151], NLRP12 [152], NLRC4 [145,153], and AIM2 [153], as detailed below.…”