Necrostatin-1 protects hippocampal neurons against ischemia/reperfusion injury via the RIP3/DAXX signaling pathway in rats

Yang, Ru; Hu, Kun; Chen, Jieyun; Zhu, Shenglong; Li, Lei; Lu, Hailong; Li, Pingjing; Dong, Rong

doi:10.1016/j.neulet.2017.05.016

Cited by 43 publications

(31 citation statements)

References 30 publications

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“…Phosphorylated MLKL subsequently forms pores in the plasma membrane, leading to neuronal death and release of proinflammatory factors from the cell. Several reports indicate that RIPK signaling contributes to neuronal loss in various in vivo mod-els (Ito et al 2016;Caccamo et al 2017;Yang et al 2017;Zhang et al 2017;Iannielli et al 2018). In some studies, RIPK1 has been shown to act directly in neurons to regulate degeneration (Re et al 2014;Iannielli et al 2018;Arrazola et al 2019), whereas others suggest that RIPK1 regulates necroptosis in other central nervous system cell types (Ofengeim et al 2015;Ito et al 2016).…”

Section: Evidence For Apoptosis Necroptosis and Other Death Pathwaymentioning

confidence: 99%

“…Genentech/Roche has advanced the first DLK inhibitor into clinical trials for ALS (NCT02655614), although results have not yet been reported. In the case of RIPK1, preclinical data from genetic models and mice treated with RIPK1 inhibitors, including necrostatin-1, suggest a potential role for RIPK1 signaling in a number of disease contexts, including AD, ALS, and multiple sclerosis (Re et al 2014;Ofengeim et al 2015Ofengeim et al , 2017Yang et al 2017;Arrazola et al 2019). Denali Therapeutics has recently advanced a CNS penetrant RIPK1 inhibitor into clinical trials, which is being tested in patients with AD and ALS (NCT03757325, NCT03757351).…”

Section: Cell Death and Neurodegenerationmentioning

confidence: 99%

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Cell Death and Neurodegeneration

Andreone

Larhammar

Lewcock

2019

Cold Spring Harb Perspect Biol

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Section: Evidence For Apoptosis Necroptosis and Other Death Pathwaymentioning

confidence: 99%

Section: Cell Death and Neurodegenerationmentioning

confidence: 99%

Cell Death and Neurodegeneration

Andreone

Larhammar

Lewcock

2019

Cold Spring Harb Perspect Biol

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“…Among them, necrostatin-1 (Nec-1; methyl-thiohydantoin-tryptophan) was the first to be identified and since then used the most frequently (Degterev et al 2005(Degterev et al , 2008. The neuroprotective potential of Nec-1 and its analogs in cellular and animal models of ischemia is rather well supported (Chavez-Valdez et al 2012Degterev et al 2005;Li et al 2018;Ni et al 2018;Northington et al 2011;Xu et al 2010a;Yang et al 2017a;Yin et al 2015;Zhan et al 2019;Zhang et al 2016). Moreover, in an in vitro setting, Nec-1 attenuated the neuronal cell damage induced by various harmful agents, e.g., oaubain, glutamate (Glu), N-methyl-D-aspartate (NMDA), 6hydroxydopamine (6-OHDA), rotenone, 1-methyl-4phenylpyridinium ion (MPP+), methamphetamine, aluminum (Al), 24(S)-hydroxycholesterol, cholesterol, staurosporine, and doxorubicin (Funakoshi et al 2016;Ito et al 2017;Jantas et al 2014a;Li et al 2011;Wang et al 2014;Wu et al 2015;Xiong et al 2016;Xu et al 2007;Yamanaka et al 2011;Zhang et al 2013).…”

Section: Introductionmentioning

confidence: 99%

Neuroprotective Effects of Necrostatin-1 Against Oxidative Stress–Induced Cell Damage: an Involvement of Cathepsin D Inhibition

et al. 2020

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Necroptosis, a recently discovered form of non-apoptotic programmed cell death, can be implicated in many pathological conditions including neuronal cell death. Moreover, an inhibition of this process by necrostatin-1 (Nec-1) has been shown to be neuroprotective in in vitro and in vivo models of cerebral ischemia. However, the involvement of this type of cell death in oxidative stress-induced neuronal cell damage is less recognized. Therefore, we tested the effects of Nec-1, an inhibitor of necroptosis, in the model of hydrogen peroxide (H 2 O 2)-induced cell damage in human neuroblastoma SH-SY5Y and murine hippocampal HT-22 cell lines. The data showed that Nec-1 (10-40 μM) attenuated the cell death induced by H 2 O 2 in undifferentiated (UN-) and neuronal differentiated (RA-) SH-SY5Y cells with a higher efficacy in the former cell type. Moreover, Nec-1 partially reduced cell damage induced by 6-hydroxydopamine in UN-and RASH -SY5Y cells. The protective effect of Nec-1 was of similar magnitude as the effect of a caspase-3 inhibitor in both cell phenotypes and this effect were not potentiated after combined treatment. Furthermore, the non-specific apoptosis and necroptosis inhibitor curcumin augmented the beneficial effect of Nec-1 against H 2 O 2-evoked cell damage albeit only in RASH -SY5Y cells. Next, it was found that the mechanisms of neuroprotective effect of Nec-1 against H 2 O 2induced cell damage in SH-SY5Y cells involved the inhibition of lysosomal protease, cathepsin D, but not caspase-3 or calpain activities. In HT-22 cells, Nec-1 was protective in two models of oxidative stress (H 2 O 2 and glutamate) and that effect was blocked by a caspase inhibitor. Our data showed neuroprotective effects of the necroptosis inhibitor, Nec-1, against oxidative stress-induced cell damage and pointed to involvement of cathepsin D inhibition in the mechanism of its action. Moreover, a cell type-specific interplay between necroptosis and apoptosis has been demonstrated.

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“…The inhibition of necroptosis may also provide effective relief from the symptoms of MS. Previous studies have illustrated that Nec-1 has a significant neuroprotective effect in ischemic stroke (6,42,43). However, the role of Nec-1 in MS remains unknown.…”

Section: Discussionmentioning

confidence: 99%

“…Necrostatin-1 (Nec-1) is a potent and specific inhibitor of necroptosis that allosterically suppresses the activity of receptor-interacting serine/threonine protein kinase (RIPK)1, blocking formation of the RIPK1-RIPK3 complex (5). The protective effects of Nec-1 have been reported in a number of experimental models, including models of ischemic brain injury, inflammatory kidney disease, myocardial infarction, Parkinson's disease and various types of cancer (6)(7)(8)(9)(10)(11). However, the effects of Nec-1 in MS remain unknown.…”

Section: Introductionmentioning

confidence: 99%

Necrostatin‑1 ameliorates the pathogenesis of experimental autoimmune encephalomyelitis by suppressing apoptosis and necroptosis of oligodendrocyte precursor cells

et al. 2019

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Multiple sclerosis (MS) is an autoimmune disease of the central nervous system characterized by neuronal demyelination. MS pathogenesis occurs via multiple mechanisms, and is mediated in part by oligodendrocyte apoptosis and a robust inflammatory response. In the present study, Necrostatin-1 (Nec-1), a specific inhibitor of the receptor-interacting protein 1 kinase domain, was revealed to effectively alleviate the severity and pathological damage associated with experimental autoimmune encephalomyelitis (EAE), a commonly used mouse model of MS. In addition, treatment with Nec-1 significantly decreased the number of lesions and inflammatory cell infiltrates in spinal cord tissues, as well as the production of associated pro-inflammatory cytokines, including tumor necrosis factor α (TNFα), interferon-γ and interleukin-1β. Nec-1 also suppressed TNFα + zVAD-fmk-induced apoptosis and necroptosis in primary oligodendrocyte precursor cells. The present study revealed that Nec-1 effectively attenuated the progression of EAE by suppressing apoptosis and necroptosis in oligodendrocytes, and represents a potential novel therapeutic agent for the treatment of MS.

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Necrostatin-1 protects hippocampal neurons against ischemia/reperfusion injury via the RIP3/DAXX signaling pathway in rats

Cited by 43 publications

References 30 publications

Cell Death and Neurodegeneration

Cell Death and Neurodegeneration

Neuroprotective Effects of Necrostatin-1 Against Oxidative Stress–Induced Cell Damage: an Involvement of Cathepsin D Inhibition

Necrostatin‑1 ameliorates the pathogenesis of experimental autoimmune encephalomyelitis by suppressing apoptosis and necroptosis of oligodendrocyte precursor cells

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