Necrostatin-1 Improves Long-term Functional Recovery Through Protecting Oligodendrocyte Precursor Cells After Transient Focal Cerebral Ischemia in Mice

Chen, Yingzhu; Zhang, Lingling; Yu, Hailong; Song, Kangping; Shi, Jinling; Chen, Linlin; Cheng, Jian

doi:10.1016/j.neuroscience.2017.12.007

Cited by 53 publications

(34 citation statements)

References 45 publications

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“…Intracerebroventricular administration of Nec-1 was shown to reduce the infarct volume in MCAO, with an extended time window for neuroprotection (2). Subsequent studies supported the protective effect of inhibiting RIPK1 kinase in ischemic injuries induced in multiple tissues/organs, including brain, eye, heart, and kidney (24)(25)(26)(27)(28)(29)(30)(31). While these studies highlighted the important role of RIPK1 as a central mediator of brain damage following acute ischemic neuronal injury, how the activation of RIPK1 mediates tissue injuries and cell death remains unclear.…”

Section: Discussionmentioning

confidence: 95%

Sequential activation of necroptosis and apoptosis cooperates to mediate vascular and neural pathology in stroke

Naito

Amin

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

111

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Apoptosis and necroptosis are two regulated cell death mechanisms; however, the interaction between these cell death pathways in vivo is unclear. Here we used cerebral ischemia/reperfusion as a model to investigate the interaction between apoptosis and necroptosis. We show that the activation of RIPK1 sequentially promotes necroptosis followed by apoptosis in a temporally specific manner. Cerebral ischemia/reperfusion insult rapidly activates necroptosis to promote cerebral hemorrhage and neuroinflammation.Ripk3deficiency reduces cerebral hemorrhage and delays the onset of neural damage mediated by inflammation. Reduced cerebral perfusion resulting from arterial occlusion promotes the degradation of TAK1, a suppressor of RIPK1, and the transition from necroptosis to apoptosis. Conditional knockout of TAK1 in microglial/infiltrated macrophages and neuronal lineages sensitizes to ischemic infarction by promoting apoptosis. Taken together, our results demonstrate the critical role of necroptosis in mediating neurovascular damage and hypoperfusion-induced TAK1 loss, which subsequently promotes apoptosis and cerebral pathology in stroke and neurodegeneration.

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Section: Discussionmentioning

confidence: 95%

Sequential activation of necroptosis and apoptosis cooperates to mediate vascular and neural pathology in stroke

Naito

Amin

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

111

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“…The RIPK3 inhibitor dabrafenib protected against focal ischemic brain injury in mice (120). RIPK1 was associated with neuroinflammation and neural cell death in rodent models of MCAO-induced stroke (121)(122)(123). The RIPK1 inhibitors necrostatin-1 and 5-(3',5'-dimethoxybenzal)-2-thio-imidazole-4-ketone (DTIO) conferred protection in models of stroke by limiting neuronal injury and death (120)(121)(122)(123)(124).…”

Section: Necroptosis and Cardiovascular Diseasementioning

confidence: 99%

Necroptosis: a crucial pathogenic mediator of human disease

et al. 2019

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Conflict of interest: AMKC is a cofounder of, is a stockholder of, and serves on the Scientific Advisory Board for Proterris, Inc., which develops therapeutic uses for carbon monoxide. AMKC also has a use patent (US 7,678,390) on CO. AMKC served as a consultant for Teva Pharmaceuticals in July 2018. The spouse of MEC is a cofounder of, is a shareholder of, and serves on the Scientific Advisory Board of Proterris, Inc.

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“…Multiple studies using genetic or pharmacological inhibition have identified RIPK1 kinase activity-dependent cell death as a potent trigger of inflammation in different tissues [13][14][15][16][17] . Furthermore, RIPK1 kinase activity emerged as driver of ischemic injury [18][19][20] as well as neurodegenerative diseases such as multiple sclerosis (MS) 21 , ALS (amyotrophic lateral sclerosis) 22 and Alzheimer's disease 23 . These studies identified RIPK1 kinase activity as a key factor contributing to the pathogenesis of inflammatory diseases, prompting the development of RIPK1 kinase inhibitors [24][25][26][27][28] that reached clinical trials for the treatment of inflammatory and neurodegenerative diseases as well as pancreatic cancer 24,25 .…”

mentioning

confidence: 99%

Autophosphorylation at serine 166 regulates RIP kinase 1-mediated cell death and inflammation

et al. 2020

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Receptor interacting protein kinase 1 (RIPK1) regulates cell death and inflammatory responses downstream of TNFR1 and other receptors, and has been implicated in the pathogenesis of inflammatory and degenerative diseases. RIPK1 kinase activity induces apoptosis and necroptosis, however the mechanisms and phosphorylation events regulating RIPK1dependent cell death signaling remain poorly understood. Here we show that RIPK1 autophosphorylation at serine 166 plays a critical role for the activation of RIPK1 kinase-dependent apoptosis and necroptosis. Moreover, we show that S166 phosphorylation is required for RIPK1 kinase-dependent pathogenesis of inflammatory pathologies in vivo in four relevant mouse models. Mechanistically, we provide evidence that trans autophosphorylation at S166 modulates RIPK1 kinase activation but is not by itself sufficient to induce cell death. These results show that S166 autophosphorylation licenses RIPK1 kinase activity to induce downstream cell death signaling and inflammation, suggesting that S166 phosphorylation can serve as a reliable biomarker for RIPK1 kinase-dependent pathologies.

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Necrostatin-1 Improves Long-term Functional Recovery Through Protecting Oligodendrocyte Precursor Cells After Transient Focal Cerebral Ischemia in Mice

Cited by 53 publications

References 45 publications

Sequential activation of necroptosis and apoptosis cooperates to mediate vascular and neural pathology in stroke

Sequential activation of necroptosis and apoptosis cooperates to mediate vascular and neural pathology in stroke

Necroptosis: a crucial pathogenic mediator of human disease

Autophosphorylation at serine 166 regulates RIP kinase 1-mediated cell death and inflammation

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