Inhibition of microglial receptor‐interacting protein kinase 1 ameliorates neuroinflammation following cerebral ischaemic stroke

Jiao, Yang; Wang, Jianjian; Zhang, Huixue; Cao, Yuze; Qu, Yang; Huang, Siyu; Kong, Xiaotong; Song, Chang Eun; Li, Jie; Li, Qian; Ma, Heping; Lu, Xiaoyu; Wang, Lihua

doi:10.1111/jcmm.15820

Cited by 25 publications

(15 citation statements)

References 46 publications

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“…RIPK1 is upregulated in rat brain upon MCAO and localized to the microglia. Furthermore, RIPK1 triggers activation of NLRP3 inflammasome by disrupting the mitochondrial membrane integrity and by promoting mtROS release in ischemic microglia ( 140 ). As the first selective inhibitor, necrostatin-1 (Nec-1) significantly decreased RIPK1 phosphorylation in rat brain following ischemic stroke.…”

Section: Mitochondria Regulate Nlrp3 Inflammasome Activation During I...mentioning

confidence: 99%

Focus on the role of mitochondria in NLRP3 inflammasome activation: A prospective target for the treatment of ischemic stroke (Review)

et al. 2022

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Post-ischemic neuroinflammation induced by the innate local immune response is a major pathophysiological feature of cerebral ischemic stroke, which remains the leading cause of mortality and disability worldwide. NLR family pyrin domain containing (NLRP)3 inflammasome crucially mediates post-ischemic inflammatory responses via its priming, activation and interleukin-1β release during hypoxic-ischemic brain damage. Mitochondrial dysfunctions are among the main hallmarks of several brain diseases, including ischemic stroke. In the present review, focus was addressed on the role of mitochondria in cerebral ischemic stroke while keeping NLRP3 inflammasome as a link. Under ischemia and hypoxia, mitochondria are capable of controlling NLRP3 inflammasome-mediated neuroinflammation through mitochondrial released contents, mitochondrial localization and mitochondrial related proteins. Thus, inflammasome and mitochondria may be attractive targets to treat ischemic stroke as well as the several drugs that target the process of mitochondrial function to treat cerebral ischemic stroke. At present, certain drugs have already been studied in clinical trials.

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Section: Mitochondria Regulate Nlrp3 Inflammasome Activation During I...mentioning

confidence: 99%

Focus on the role of mitochondria in NLRP3 inflammasome activation: A prospective target for the treatment of ischemic stroke (Review)

et al. 2022

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“…However, reperfusion processes after ischemic attack may further exacerbate brain damage, which is named cerebral ischemia/reperfusion (I/R) injury [5,6]. It is increasingly understood that multiple pathophysiological processes, includ-ing oxidative stress, the inflammatory response, neuronal death, and apoptosis, play a pivotal role in the development of cerebral I/R injury [7][8][9][10]. Thus, treatments based on the above mechanisms are proposed as a promising strategy to attenuate the outcomes of stroke and cerebral I/R injury.…”

Section: Introductionmentioning

confidence: 99%

Palmatine Protects against Cerebral Ischemia/Reperfusion Injury by Activation of the AMPK/Nrf2 Pathway

Tang

Hong

et al. 2021

Oxidative Medicine and Cellular Longevity

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Palmatine (PAL), a natural isoquinoline alkaloid, possesses extensive biological and pharmaceutical activities, including antioxidative stress, anti-inflammatory, antitumor, neuroprotective, and gastroprotective activities. However, it is unknown whether PAL has a protective effect against ischemic stroke and cerebral ischemia/reperfusion (I/R) injury. In the present study, a transient middle cerebral artery occlusion (MCAO) mouse model was used to mimic ischemic stroke and cerebral I/R injury in mice. Our study demonstrated that PAL treatment ameliorated cerebral I/R injury by decreasing infarct volume, neurological scores, and brain water content. PAL administration attenuated oxidative stress, the inflammatory response, and neuronal apoptosis in mice after cerebral I/R injury. In addition, PAL treatment also decreases hypoxia and reperfusion- (H/R-) induced neuronal injury by reducing oxidative stress, the inflammatory response, and neuronal apoptosis. Moreover, the neuroprotective effects of PAL were associated with the activation of the AMP-activated protein kinase (AMPK)/nuclear factor E2-related factor 2 (Nrf2) pathway, and Nrf2 knockdown offsets PAL-mediated antioxidative stress and anti-inflammatory effects. Therefore, our results suggest that PAL may be a novel treatment strategy for ischemic stroke and cerebral I/R injury.

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“…This directly proved that RIP1 inhibition could act on mitochondria and suppress ROS generation after OGD/R in retina cells [98]. In another study in mouse BV2 microglia cells, Nec-1 partially reversed the OGD-induced cell damage, which was associated with improved mitochondrial function, attenuated ROS level, decreased apoptosis rate, inhibited inflammasome activation (NLPR3, ASC, caspase-1), reduced inflammatory mediators (TNFα, IL-1β and MMP-9) and increased TGFβ level [99]. The above-mentioned effects of Nec-1 were comparable to those of recombinant human thioredoxin-1 (rhTrx-1), which has been shown in molecular docking studies to inhibit RIP1 kinase.…”

Section: Neuroprotective Effects Of Necroptosis Inhibitors In In Vitro Ischemia/hypoxia Modelsmentioning

confidence: 91%

“…Direct evidence for the association between necroptosis and oxidative stress was provided by Jiao et al [99], who in the transient MCAO (middle cerebral artery occlusion) model in mice showed neuroprotective effects of rhTrx-1, an antioxidant and antiinflammatory agent [127]. This effect was associated with attenuation of ischemia-induced RIP1 expression and occurrence of Iba1+/RIP1+cells, pointing to an involvement of necroptosis and showing that microglia cells are an important player in the rhTrx-mediated protection.…”

Section: In Vivo Studies Linking Oxidative Stress and Necroptosis In Relation To Neurodegenerative Diseasesmentioning

confidence: 93%

“…The above-mentioned effects of Nec-1 were comparable to those of recombinant human thioredoxin-1 (rhTrx-1), which has been shown in molecular docking studies to inhibit RIP1 kinase. Moreover, rhTrx-1 attenuated the increased OGD cell damage rate observed in co-culture of HT-22 with BV2 cells when compared to neuronal cell culture, suggesting a predominant role of microglial RIP1 in OGD-induced necroptosis in these cellular models [99]. Another OGD study showed a critical role of necroptosis in regulating ROS by knockdown RIP1 expression in BV2 cells with or without PGRN (progranulin) silence [100].…”

Section: Neuroprotective Effects Of Necroptosis Inhibitors In In Vitro Ischemia/hypoxia Modelsmentioning

confidence: 94%

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Preclinical Evidence for the Interplay between Oxidative Stress and RIP1-Dependent Cell Death in Neurodegeneration: State of the Art and Possible Therapeutic Implications

Jantas

Lasoń

2021

Antioxidants

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Neurodegenerative diseases are the most frequent chronic, age-associated neurological pathologies having a major impact on the patient’s quality of life. Despite a heavy medical, social and economic burden they pose, no causative treatment is available for these diseases. Among the important pathogenic factors contributing to neuronal loss during neurodegeneration is elevated oxidative stress resulting from a disturbed balance between endogenous prooxidant and antioxidant systems. For many years, it was thought that increased oxidative stress was a cause of neuronal cell death executed via an apoptotic mechanism. However, in recent years it has been postulated that rather programmed necrosis (necroptosis) is the key form of neuronal death in the course of neurodegenerative diseases. Such assumption was supported by biochemical and morphological features of the dying cells as well as by the fact that various necroptosis inhibitors were neuroprotective in cellular and animal models of neurodegenerative diseases. In this review, we discuss the relationship between oxidative stress and RIP1-dependent necroptosis and apoptosis in the context of the pathomechanism of neurodegenerative disorders. Based on the published data mainly from cellular models of neurodegeneration linking oxidative stress and necroptosis, we postulate that administration of multipotential neuroprotectants with antioxidant and antinecroptotic properties may constitute an efficient pharmacotherapeutic strategy for the treatment of neurodegenerative diseases.

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Inhibition of microglial receptor‐interacting protein kinase 1 ameliorates neuroinflammation following cerebral ischaemic stroke

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 25 publications

References 46 publications

Focus on the role of mitochondria in NLRP3 inflammasome activation: A prospective target for the treatment of ischemic stroke (Review)

Focus on the role of mitochondria in NLRP3 inflammasome activation: A prospective target for the treatment of ischemic stroke (Review)

Palmatine Protects against Cerebral Ischemia/Reperfusion Injury by Activation of the AMPK/Nrf2 Pathway

Preclinical Evidence for the Interplay between Oxidative Stress and RIP1-Dependent Cell Death in Neurodegeneration: State of the Art and Possible Therapeutic Implications

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