The pivotal role of the NLRC4 inflammasome in neuroinflammation after intracerebral hemorrhage in rats

Gan, Hui; Zhang, Li; Chen, Hui; Xiao, Han; Wang, Lu; Zhai, Xuan; Jiang, Ning; Liang, Ping; Zheng, Shuyue; Zhao, Jing

doi:10.1038/s12276-021-00702-y

Cited by 21 publications

(22 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The activation of inflammasomes increases cytotoxicity and contributes to the pyroptosis of neurons, which is a key factor for memory loss and cognitive impairment [ 27 ]. For instance, the activation of NLRC4 inflammasome interacts with CASP1, IL-1 β , and p-Tau to contribute to neuroinflammation and memory impairment [ 28 ]. High levels of caspase1 induces human mild cognitive impairment and brain functions in patients with Alzheimer's disease, while depletion of NLRP3 promotes spatial memory and suppresses M2 polarization of microglia and deposition of amyloid- β [ 29 ].…”

Section: Discussionmentioning

confidence: 99%

Lactobacillus pentosus Alleviates Lipopolysaccharide-Induced Neuronal Pyroptosis via Promoting BIRC3-Mediated Inactivation of NLRC4

Shao²

2022

Evidence-Based Complementary and Alternative Medicine

View full text Add to dashboard Cite

Objective. Neurodegenerative disease is a common neurodegenerative disorder. Lactobacillus pentosus (L. pentosus) plays a neuron-protective role. This study aimed to investigate the effects of L. pentosus on neurodegenerative diseases. Methods. Cells were treated with lipopolysaccharide (LPS) to establish neurodegenerative diseases model in vivo and with L. pentosus strain S-PT84. Reverse transcription-quantitative PCR (RT-qPCR) was applied to determine mRNA levels. Western blot was performed to detect protein expression. Cellular behaviors were detected using Cell Counting Kit-8 (CCK-8), flow cytometry, and TdT-mediated dUTP nick-end labeling (TUNEL) assay. The interaction between baculoviral IAP repeat containing 3 (BIRC3) and NLR family CARD domain containing 4 (NLRC4) was predicted by STING and verified by western blot. Result. L. pentosus suppressed LPS-induced pyroptosis and promoted the cell viability of neurons. Additionally, L. pentosus suppressed the release of proinflammatory cytokines (interleukin 1 beta (IL-1β) and IL-18) and the protein expression of pyroptosis biomarkers (cleaved caspase1 (CL-CASP1) and N-terminal fragment gasdermin D (GSDMD-N)). Moreover, L. pentosus upregulated BIRC3, which induced the inactivation of NLRC4. However, BIRC3 knockdown alleviated the effects of L. pentosus and induced neuronal degeneration. Conclusion. L. pentosus may play a neuron-protective role via regulating BIRC3/NLRC4 signaling pathways. Therefore, L. pentosus may be a promising strategy for neurodegenerative diseases.

show abstract

Section: Discussionmentioning

confidence: 99%

Lactobacillus pentosus Alleviates Lipopolysaccharide-Induced Neuronal Pyroptosis via Promoting BIRC3-Mediated Inactivation of NLRC4

Shao²

2022

Evidence-Based Complementary and Alternative Medicine

View full text Add to dashboard Cite

show abstract

“…Similarly to NLRP3 and NLRP1, NLRC4 amplifies inflammation by facilitating the processing of caspase-1, IL-1β, IL-18, and TNF-α. Furthermore, elimination of NLRC4 attenuates neuronal death, BBB damage, brain edema, and neurological deficiency 3 days after ICH ( 84 ). Therefore, it is essential to explore the role of the two pathways in pyroptosis after ICH and to see if they are related to the NLRP3/caspase-1 pathway.…”

Section: Potential Mechanisms Of Pyroptosis After Ichmentioning

confidence: 99%

Perspectives on the mechanism of pyroptosis after intracerebral hemorrhage

et al. 2022

View full text Add to dashboard Cite

Intracerebral hemorrhage (ICH) is a highly harmful neurological disorder with high rates of mortality, disability, and recurrence. However, effective therapies are not currently available. Secondary immune injury and cell death are the leading causes of brain injury and a poor prognosis. Pyroptosis is a recently discovered form of programmed cell death that differs from apoptosis and necrosis and is mediated by gasdermin proteins. Pyroptosis is caused by multiple pathways that eventually form pores in the cell membrane, facilitating the release of inflammatory substances and causing the cell to rupture and die. Pyroptosis occurs in neurons, glial cells, and endothelial cells after ICH. Furthermore, pyroptosis causes cell death and releases inflammatory factors such as interleukin (IL)-1β and IL-18, leading to a secondary immune-inflammatory response and further brain damage. The NOD-like receptor protein 3 (NLRP3)/caspase-1/gasdermin D (GSDMD) pathway plays the most critical role in pyroptosis after ICH. Pyroptosis can be inhibited by directly targeting NLRP3 or its upstream molecules, or directly interfering with caspase-1 expression and GSDMD formation, thus significantly improving the prognosis of ICH. The present review discusses key pathological pathways and regulatory mechanisms of pyroptosis after ICH and suggests possible intervention strategies to mitigate pyroptosis and brain dysfunction after ICH.

show abstract

“…Although NLRP3 in the NLRs family is the most characteristic inflammatory body sensor, numerous additional sensors, shown in Figure 1, including NLRP1, NLRC4, NLRP6, and AIM2 in ALRs, can also generate inflammasomes and engage in the control of host immunological and inflammatory responses (Broz and Dixit, 2016;Kay et al, 2020). In ICH, NLRP1, NLRP3, NLRP6, NLRC4, etc., are mostly studied, as shown in Supplementary Table 1 (Yao et al, 2017;Chen et al, 2019c;Xiao et al, 2020;Gan et al, 2021;Yan et al, 2021). Then, we'll go through various inflammasome subtypes that were present in ICH.…”

Section: Pyroptosis and Pyroptotic-associated Protein Inflammasomementioning

confidence: 99%

“…In models of ICH, activation of inflammatory bodies (NLRP1, NLRP3, NLRC4) and activation of the pathway of caspase-1/GSDMDmediated pyroptosis is considered the most common cause of neurological deficits. (Yao et al, 2017;Gan et al, 2021;Yan et al, 2021).…”

Section: Canonical Pyroptotic Pathway Dependent On Caspase-1mentioning

confidence: 99%

See 1 more Smart Citation

Microglial pyroptosis: Therapeutic target in secondary brain injury following intracerebral hemorrhage

Sun

et al. 2022

Front. Cell. Neurosci.

View full text Add to dashboard Cite

Intracerebral hemorrhage (ICH) is a major cerebrovascular illness that causes substantial neurological sequelae and dysfunction caused by secondary brain injury (SBI), and there are no effective therapies to mitigate the disability. Microglia, the brain-resident macrophage, participates in the primary inflammatory response, and activation of microglia to an M1-like phenotype largely takes place in the acute phase following ICH. A growing body of research suggests that the pathophysiology of SBI after ICH is mediated by an inflammatory response mediated by microglial-pyroptotic inflammasomes, while inhibiting the activation of microglial pyroptosis could suppress the inflammatory cascade reaction, thus attenuating the brain injury after ICH. Pyroptosis is characterized by rapid plasma membrane disruption, followed by the release of cellular contents and pro-inflammatory mediators. In this review, we outline the molecular mechanism of microglial pyroptosis and summarize the up-to-date evidence of its involvement in the pathological process of ICH, and highlight microglial pyroptosis-targeted strategies that have the potential to cure intracerebral hemorrhage. This review contributes to a better understanding of the function of microglial pyroptosis in ICH and assesses it as a possible therapeutic target.

show abstract

The pivotal role of the NLRC4 inflammasome in neuroinflammation after intracerebral hemorrhage in rats

Cited by 21 publications

References 54 publications

Lactobacillus pentosus Alleviates Lipopolysaccharide-Induced Neuronal Pyroptosis via Promoting BIRC3-Mediated Inactivation of NLRC4

Lactobacillus pentosus Alleviates Lipopolysaccharide-Induced Neuronal Pyroptosis via Promoting BIRC3-Mediated Inactivation of NLRC4

Perspectives on the mechanism of pyroptosis after intracerebral hemorrhage

Microglial pyroptosis: Therapeutic target in secondary brain injury following intracerebral hemorrhage

Contact Info

Product

Resources

About