Immunoproteasome modulates NLRP3 inflammasome‐mediated neuroinflammation under cerebral ischaemia and reperfusion conditions

Chen, Xingyong; Wang, Yinzhou; Yao, Nannan; Lin, Zejing

doi:10.1111/jcmm.17104

Cited by 14 publications

(6 citation statements)

References 25 publications

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“…393 An in vitro study revealed that treatment modulating the immunoproteasome/NF-κB/NLRP3 inflammasome signaling axis could work against hypoxia and ischemia, as well as prevent apoptosis. 394 Therefore, inhibition of NLRP3 inflammasome formation could possibly attenuate ischemic stroke inflammatory processes and limit cell death.…”

Section: Pathophysiology and Signaling Pathways Involved In Ischemic ...mentioning

confidence: 99%

Signaling pathways involved in ischemic stroke: molecular mechanisms and therapeutic interventions

Qin

Yang

Chu

et al. 2022

Sig Transduct Target Ther

240

130

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Ischemic stroke is caused primarily by an interruption in cerebral blood flow, which induces severe neural injuries, and is one of the leading causes of death and disability worldwide. Thus, it is of great necessity to further detailly elucidate the mechanisms of ischemic stroke and find out new therapies against the disease. In recent years, efforts have been made to understand the pathophysiology of ischemic stroke, including cellular excitotoxicity, oxidative stress, cell death processes, and neuroinflammation. In the meantime, a plethora of signaling pathways, either detrimental or neuroprotective, are also highly involved in the forementioned pathophysiology. These pathways are closely intertwined and form a complex signaling network. Also, these signaling pathways reveal therapeutic potential, as targeting these signaling pathways could possibly serve as therapeutic approaches against ischemic stroke. In this review, we describe the signaling pathways involved in ischemic stroke and categorize them based on the pathophysiological processes they participate in. Therapeutic approaches targeting these signaling pathways, which are associated with the pathophysiology mentioned above, are also discussed. Meanwhile, clinical trials regarding ischemic stroke, which potentially target the pathophysiology and the signaling pathways involved, are summarized in details. Conclusively, this review elucidated potential molecular mechanisms and related signaling pathways underlying ischemic stroke, and summarize the therapeutic approaches targeted various pathophysiology, with particular reference to clinical trials and future prospects for treating ischemic stroke.

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Section: Pathophysiology and Signaling Pathways Involved In Ischemic ...mentioning

confidence: 99%

Signaling pathways involved in ischemic stroke: molecular mechanisms and therapeutic interventions

Qin

Yang

Chu

et al. 2022

Sig Transduct Target Ther

240

130

View full text Add to dashboard Cite

show abstract

“…Post-mortem analysis of stroke patient’s brains showed higher expression of NLRP3 and caspase-1 along with IL-1 and IL-18 . Similarly, a recent study has demonstrated a 4-fold increase in NLRP3 protein levels in rat brains subjected to ischemic stroke . The NLRP3 expression was mainly observed in the cytoplasm of microglia astrocytes and neurons in the area surrounding the infarct core .…”

Section: Role Of Nlrp3 In Strokementioning

confidence: 94%

“…Similarly, a recent study has demonstrated a 4-fold increase in NLRP3 protein levels in rat brains subjected to ischemic stroke . The NLRP3 expression was mainly observed in the cytoplasm of microglia astrocytes and neurons in the area surrounding the infarct core . Franke et al also found that NLRP3 and other NLRP3 inflammasome-related genes were upregulated within 24 h after stroke .…”

Section: Role Of Nlrp3 In Strokementioning

confidence: 95%

Role of NLRP3 Inflammasome in Stroke Pathobiology: Current Therapeutic Avenues and Future Perspective

Panbhare,

Pandey,

Chauhan

et al. 2023

ACS Chem. Neurosci.

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Neuroinflammation is a key pathophysiological feature of stroke-associated brain injury. A local innate immune response triggers neuroinflammation following a stroke via activating inflammasomes. The nucleotide-binding oligomerization domain leucine-rich repeat and pyrin domain-containing protein 3 (NLRP3) inflammasome has been heavily implicated in stroke pathobiology. Following a stroke, several stimuli have been suggested to trigger the assembly of the NLRP3 inflammasome. Recent studies have advanced the understanding and revealed several new players regulating NLRP3 inflammasome-mediated neuroinflammation. This article discussed recent advancements in NLRP3 assembly and highlighted stroke-induced mitochondrial dysfunction as a major checkpoint to regulating NLRP3 activation. The NLRP3 inflammasome activation leads to caspase-1-dependent maturation and release of IL-1β, IL-18, and gasdermin D. In addition, genetic or pharmacological inhibition of the NLRP3 inflammasome activation and downstream signaling has been shown to attenuate brain infarction and improve the neurological outcome in experimental models of stroke. Several drug-like small molecules targeting the NLRP3 inflammasome are in different phases of development as novel therapeutics for various inflammatory conditions, including stroke. Understanding how these molecules interfere with NLRP3 inflammasome assembly is paramount for their better optimization and/or development of newer NLRP3 inhibitors. In this review, we summarized the assembly of the NLRP3 inflammasome and discussed the recent advances in understanding the upstream regulators of NLRP3 inflammasomemediated neuroinflammation following stroke. Additionally, we critically examined the role of the NLRP3 inflammasome-mediated signaling in stroke pathophysiology and the development of therapeutic modalities to target the NLRP3 inflammasome-related signaling for stroke treatment.

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“…BAY 11-7082 suppresses the phosphorylation of IκBα and NF-κB translocation to the nucleus induced by TNF-α, thereby suppressing NLRP3 inflammasome activation ( 122 ). Following oxygen-glucose deprivation and re-oxygenation, BAY 11-7082 decreases the levels of the NLRP3 inflammasome and cleaved caspase-1 protein in BV2 microglial cells, presenting a pharmacological effect in stroke ( 123 ). Moreover, chronic cold stress activates the microglia, causing neuroinflammation that can be significantly inhibited by BAY 11-7082 by targeting the GABA-induced NLRP3 inflammasome ( 124 ).…”

Section: Inhibitors Of the Nlrp3 Inflammasome Pathwaymentioning

confidence: 99%

Inhibitors of the NLRP3 inflammasome pathway as promising therapeutic candidates for inflammatory diseases (Review)

et al. 2023

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The inflammasome regulates innate immunity by serving as a signaling platform. The Nod-like receptor protein 3 (NLRP3) inflammasome, equipped with NLRP3, the adaptor protein apoptosis-associated speck-like protein (ASC) and pro-caspase-1, is by far the most extensively studied and well-characterized inflammasome. A variety of stimuli can activate the NLRP3 inflammasome. When activated, the NLRP3 protein recruits the adaptor ASC protein and activates pro-caspase-1, resulting in inflammatory cytokine maturation and secretion, which is associated with inflammation and pyroptosis. However, the aberrant activation of the NLRP3 inflammasome has been linked to various inflammatory diseases, including atherosclerosis, ischemic stroke, Alzheimer's disease, diabetes mellitus and inflammatory bowel disease. Therefore, the NLRP3 inflammasome has emerged as a promising therapeutic target for inflammatory diseases. In the present review, systematic searches were performed using 'NLRP3 inhibitor(s)' and 'inflammatory disease(s)' as key words. By browsing the literature from 2012 to 2022, 100 articles were retrieved, of which 35 were excluded as they were reviews, editorials, retracted or unavailable online, and 65 articles were included. According to the retrieved literature, the current understanding of NLRP3 inflammasome pathway activation in inflammatory diseases was summarize, and inhibitors of the NLRP3 inflammasome pathway targeting the NLRP3 protein and other inflammasome components or products were highlighted. Additionally, the present review briefly discusses the current novel efforts in clinical research.

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Immunoproteasome modulates NLRP3 inflammasome‐mediated neuroinflammation under cerebral ischaemia and reperfusion conditions

Cited by 14 publications

References 25 publications

Signaling pathways involved in ischemic stroke: molecular mechanisms and therapeutic interventions

Signaling pathways involved in ischemic stroke: molecular mechanisms and therapeutic interventions

Role of NLRP3 Inflammasome in Stroke Pathobiology: Current Therapeutic Avenues and Future Perspective

Inhibitors of the NLRP3 inflammasome pathway as promising therapeutic candidates for inflammatory diseases (Review)

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