Eicosapentaenoic acid prevents inflammation induced by acute cerebral infarction through inhibition of NLRP3 inflammasome activation

Mo, Zhihuai; Tang, Chaogang; Li, Huiqing; Lei, Jie; Zhu, Lingjuan; Kou, Li; Li, Hao; Luo, Shijian; Li, Chunyi; Chen, Wenli; Zhang, Lei

doi:10.1016/j.lfs.2019.117133

Cited by 45 publications

(37 citation statements)

References 54 publications

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“…All NLRP3 components have been found to be upregulated in the first hours and days from stroke onset [137,138]. In addition, inhibition of NLRP3-mediated neuroinflammation has been associated with the improvement of IS outcome, suggesting the NLRP3 inflammasome as a promising target for treating IS [40,[139][140][141]. As reported above, mitochondrial dysfunction contributes to the activation of the NLRP3 inflammasome in several ways: mitochondrial NAD + decrease, mitochondrial ROS overproduction, BAK/BAX macropore formation, mPTP opening, and damage-associated molecular pattern (DAMP) release [142] (Figure 1).…”

Section: Mitochondria and Inflammation During I/rmentioning

confidence: 99%

Different Roles of Mitochondria in Cell Death and Inflammation: Focusing on Mitochondrial Quality Control in Ischemic Stroke and Reperfusion

et al. 2021

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Mitochondrial dysfunctions are among the main hallmarks of several brain diseases, including ischemic stroke. An insufficient supply of oxygen and glucose in brain cells, primarily neurons, triggers a cascade of events in which mitochondria are the leading characters. Mitochondrial calcium overload, reactive oxygen species (ROS) overproduction, mitochondrial permeability transition pore (mPTP) opening, and damage-associated molecular pattern (DAMP) release place mitochondria in the center of an intricate series of chance interactions. Depending on the degree to which mitochondria are affected, they promote different pathways, ranging from inflammatory response pathways to cell death pathways. In this review, we will explore the principal mitochondrial molecular mechanisms compromised during ischemic and reperfusion injury, and we will delineate potential neuroprotective strategies targeting mitochondrial dysfunction and mitochondrial homeostasis.

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Section: Mitochondria and Inflammation During I/rmentioning

confidence: 99%

Different Roles of Mitochondria in Cell Death and Inflammation: Focusing on Mitochondrial Quality Control in Ischemic Stroke and Reperfusion

et al. 2021

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“…Isoliquiritigenin inhibits NLRP3 inflammasome activation mediated by ROS and NF-κB by promoting the antioxidant system of NRF2 and alleviates early brain damage after hemorrhage [ 78 , 170 ]. Eicosapentaenoic acid (EPA) suppresses NLRP3 inflammasome activation by obstructing G protein–coupled receptor 40 (GPR40) and G protein–coupled receptor 120 (GPR120); importantly, EPA can ameliorate apoptosis induced by acute cerebral infarction [ 203 ].…”

Section: Targeting Various Components Of Inflammasome Pathways For Ischemic Stroke Treatmentmentioning

confidence: 99%

Relevant mediators involved in and therapies targeting the inflammatory response induced by activation of the NLRP3 inflammasome in ischemic stroke

Zhao

et al. 2021

J Neuroinflammation

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The nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) family pyrin domain-containing 3 (NLRP3) inflammasome is a member of the NLR family of inherent immune cell sensors. The NLRP3 inflammasome can detect tissue damage and pathogen invasion through innate immune cell sensor components commonly known as pattern recognition receptors (PRRs). PRRs promote activation of nuclear factor kappa B (NF-κB) pathways and the mitogen-activated protein kinase (MAPK) pathway, thus increasing the transcription of genes encoding proteins related to the NLRP3 inflammasome. The NLRP3 inflammasome is a complex with multiple components, including an NAIP, CIITA, HET-E, and TP1 (NACHT) domain; apoptosis-associated speck-like protein containing a CARD (ASC); and a leucine-rich repeat (LRR) domain. After ischemic stroke, the NLRP3 inflammasome can produce numerous proinflammatory cytokines, mediating nerve cell dysfunction and brain edema and ultimately leading to nerve cell death once activated. Ischemic stroke is a disease with high rates of mortality and disability worldwide and is being observed in increasingly younger populations. To date, there are no clearly effective therapeutic strategies for the clinical treatment of ischemic stroke. Understanding the NLRP3 inflammasome may provide novel ideas and approaches because targeting of upstream and downstream molecules in the NLRP3 pathway shows promise for ischemic stroke therapy. In this manuscript, we summarize the existing evidence regarding the composition and activation of the NLRP3 inflammasome, the molecules involved in inflammatory pathways, and corresponding drugs or molecules that exert effects after cerebral ischemia. This evidence may provide possible targets or new strategies for ischemic stroke therapy.

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“…NLRP3-Q705K minor allele carriage is associated with an increased risk of stroke/transient ischaemic attack ( Kastbom et al., 2015 ). Inhibition of NLRP3 inflammasome and IL-1β improves neurological deficits, alleviates brain tissue damage ( Ito et al., 2015 ; Wang, Wang, et al., 2015 ; Lammerding et al., 2016 ; Thakkar et al., 2016 ; Hong et al., 2018 ; Ismael et al., 2018 ; Teng et al., 2018 ; Qu et al., 2019 ; Mo et al., 2020 ; Zhang, Zhao, et al., 2020 ), decreases infarct volume, and alleviates the brain oedema post-ischaemic stroke ( Yang et al., 2014 ; Zhang et al., 2014 ; Wang, Li, et al., 2015 ; Lu et al., 2016 ; Qiu et al., 2016 ; He et al., 2017 ; Chen, Xu, et al., 2018 ; Ismael et al., 2018 ; Ma et al., 2019 ).…”

Section: The Mechanism Underlying Nlrp3 Inflammasome Aggravation Of Cerebrovascular Diseasesmentioning

confidence: 99%

The Role of NLRP3 Inflammasome in Cerebrovascular Diseases Pathology and Possible Therapeutic Targets

et al. 2021

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Cerebrovascular diseases are pathological conditions involving impaired blood flow in the brain, primarily including ischaemic stroke, intracranial haemorrhage, and subarachnoid haemorrhage. The nucleotide-binding and oligomerisation (NOD) domain-like receptor (NLR) family pyrin domain (PYD)-containing 3 (NLRP3) inflammasome is a protein complex and a vital component of the immune system. Emerging evidence has indicated that the NLRP3 inflammasome plays an important role in cerebrovascular diseases. The function of the NLRP3 inflammasome in the pathogenesis of cerebrovascular diseases remains an interesting field of research. In this review, we first summarised the pathological mechanism of cerebrovascular diseases and the pathological mechanism of the NLRP3 inflammasome in aggravating atherosclerosis and cerebrovascular diseases. Second, we outlined signalling pathways through which the NLRP3 inflammasome participates in aggravating or mitigating cerebrovascular diseases. Reactive oxygen species (ROS)/nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), ROS/thioredoxin-interacting protein (TXNIP) and purinergic receptor-7 (P2X7R) signalling pathways can activate the NLRP3 inflammasome; activation of the NLRP3 inflammasome can aggravate cerebrovascular diseases by mediating apoptosis and pyroptosis. Autophagy/mitochondrial autophagy, nuclear factor E2-related factor-2 (Nrf2), interferon (IFN)-β, sirtuin (SIRT), and phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) reportedly alleviate cerebrovascular diseases by inhibiting NLRP3 inflammasome activation. Finally, we explored specific inhibitors of the NLRP3 inflammasome based on the two-step activation of the NLRP3 inflammasome, which can be developed as new drugs to treat cerebrovascular diseases.

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Eicosapentaenoic acid prevents inflammation induced by acute cerebral infarction through inhibition of NLRP3 inflammasome activation

Cited by 45 publications

References 54 publications

Different Roles of Mitochondria in Cell Death and Inflammation: Focusing on Mitochondrial Quality Control in Ischemic Stroke and Reperfusion

Different Roles of Mitochondria in Cell Death and Inflammation: Focusing on Mitochondrial Quality Control in Ischemic Stroke and Reperfusion

Relevant mediators involved in and therapies targeting the inflammatory response induced by activation of the NLRP3 inflammasome in ischemic stroke

The Role of NLRP3 Inflammasome in Cerebrovascular Diseases Pathology and Possible Therapeutic Targets

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