Microglia Pyroptosis: A Candidate Target for Neurological Diseases Treatment

Abstract

In addition to its profound implications in the fight against cancer, pyroptosis have important role in the regulation of neuronal injury. Microglia are not only central members of the immune regulation of the central nervous system (CNS), but are also involved in the development and homeostatic maintenance of the nervous system. Under various pathological overstimulation, microglia pyroptosis contributes to the massive release of intracellular inflammatory mediators leading to neuroinflammation and ultimately to neuronal damages. In addition, microglia pyroptosis lead to further neurological damage by decreasing the ability to cleanse harmful substances. The pathogenic roles of microglia in a variety of CNS diseases such as neurodegenerative diseases, stroke, multiple sclerosis and depression, and many other neurological disorders have been gradually unveiled. In the context of different neurological disorders, inhibition of microglia pyroptosis by targeting NOD-like receptor family pyrin domain containing (NLRP) 3, caspase-1 and gasdermins (GSDMs) by various chemical agents as well as natural products significantly improve the symptoms or outcome in animal models. This study will provide new ideas for immunomodulatory treatment of CNS diseases.

Remote limb ischemic postconditioning inhibits microglia pyroptosis by modulating HGF after acute ischemia stroke

“…Several studies have found that pyroptosis mainly occurs in the microglia in CNS neuroimmune diseases, 36–38 and microglia pyroptosis serves as a key executioner in cerebral ischemia 14,39 . However, knowledge about microglia pyroptosis in RIPostC after AIS has not been reported yet.…”

“…Several studies have found that pyroptosis mainly occurs in the microglia in CNS neuroimmune diseases, [36][37][38] and microglia pyroptosis serves as a key executioner in cerebral ischemia. 14,39 However, knowledge about microglia pyroptosis in RIPostC after AIS has not been reported yet. In this study, we demonstrated the first evidence that RIPostC application suppressed the GSDMD immunostaining in Iba-1-labeled microglia and protein expression of GSDMD-N in MCAO mice (Figure 2c,e).…”

ANGPTL8 as an Inflammatory Trigger Aggravated Microglial Pyroptosis in the Pathogenesis of Alzheimer’s Disease

“…The NLRP3 in ammasome is a multiprotein complex composed of NLRP3, caspase-1, and ASC that recognizes pathogen-associated molecular patterns (PAMPs) or host-derived damage-associated signaling molecules (damps) and recruits and activates the proin ammatory protease caspase-1, and activated caspase-1 cleaves IL-1β and IL-18 precursors, producing the corresponding mature cytokines [34], which in turn generate a pore-forming fragment that translocates to the plasma membrane, leading to a lytic form of pyroptosis. Pyroptosis is a novel form of regulated cell death recently implicated in the pathogenesis of multiple [35,36]. Previous studies found that Aβ formation of insoluble brils can activate the NLRP3 in ammasome.…”

What type of cell death occurs in chronic cerebral hypoperfusion? A review focusing on pyroptosis and its potential therapeutic implications

“…Current research evidence suggests that the activation of microglia pyroptosis is a significant factor in neuroinflammation and is linked to several neurological diseases, including ischemic brain injury, and neurodegenerative diseases (Wu et al, 2022). Research has discovered that the expression of NLRP3 in microglia of patients with ischemic stroke is increased, and the proteins involved in NLRP3 inflammasomes, as well as IL-1β and IL-18, are also expressed at higher levels in the mouse model of MCAO/R (Fann et al, 2013).…”