Mechanism and disease implications of necroptosis and neuronal inflammation

Oliveira, Sara R.; Amaral, Joana D.; Rodrigues, Cecília M. P.

doi:10.1038/s41419-018-0872-7

Cited by 17 publications

(18 citation statements)

References 16 publications

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“…Increasing evidence indicates that necroptosis plays a crucial role in the pathogenesis of several diseases with an inflammatory component (13). Shen et al (31) found that necroptosis is an important mechanism of neuronal death after ICH, and treatment with necrostatin-1, a specific inhibitor of RIP1, could rescue the neurons from necroptosis, revealing a potential therapeutic target for ICH.…”

Section: Discussionmentioning

confidence: 99%

“…Microglia, which are primary immune cells of the central nervous system (CNS), undergo necroptosis in various pathological processes, such as ischemic stroke (11), retinal degeneration (12), and spinal cord injury (12). Therefore, it may be beneficial to inhibit necroptosis to reduce neuroinflammation and improve neuronal survival in the context of disease, particularly in microglia (13).…”

Section: Introductionmentioning

confidence: 99%

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Melatonin Suppresses Microglial Necroptosis by Regulating Deubiquitinating Enzyme A20 After Intracerebral Hemorrhage

Sun

Fang

et al. 2019

Front. Immunol.

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Cell death is deeply involved in pathophysiology of brain injury after intracerebral hemorrhage (ICH). Necroptosis, one of the recently discovered forms of cell death, plays an important role in various diseases, including ICH. Previous studies have suggested that a considerable number of neurons undergoes necroptosis after ICH. However, necroptosis of microglia after ICH has not been reported to date. The present study demonstrated for the first time that necroptosis occurred in the microglia surrounding the hematoma after ICH in C57 mice, and melatonin, a hormone that is predominantly synthesized in and secreted from the pineal gland, exerted a neuroprotective effect by suppressing this process. When we further explored the potential underlying mechanism, we found that melatonin inhibits RIP3-mediated necroptosis by regulating the deubiquitinating enzyme A20 (also known as TNFAIP3) expression after ICH. In summary, we have demonstrated the role of microglial necroptosis in the pathogenesis of ICH. More importantly, A20 was identified as a novel target of melatonin, which opens perspectives for future research.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Melatonin Suppresses Microglial Necroptosis by Regulating Deubiquitinating Enzyme A20 After Intracerebral Hemorrhage

Sun

Fang

et al. 2019

Front. Immunol.

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“…The process of necroptosis is controlled in an apoptosis‐deficient environment by receptor‐interacting proteins 1 (RIP1) and 3 (RIP3). The most understood pathway of activation of necroptosis is mediated by death receptors (Oliveira et al, ), most often by tumour necrosis factor receptor 1 (TNFR1), although the tumour necrosis factor‐related apoptosis‐inducing ligand (TRAIL) and Fas receptors can also induce necroptosis (Holler et al, ; Degterev et al, ). When a ligand binds to TNFR1, it recruits pro‐survival complex I, which consists of TNFR‐associated death domain (TRADD) and RIP1 and several ubiquin E3 ligases.…”

Section: Necroptosis: a Mechanism Of Regulated Necrotic Deathmentioning

confidence: 99%

Cell death: a review of the major forms of apoptosis, necrosis and autophagy

D'Arcy

2019

Cell Biology International

1,476

961

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Cell death was once believed to be the result of one of two distinct processes, apoptosis (also known as programmed cell death) or necrosis (uncontrolled cell death); in recent years, however, several other forms of cell death have been discovered highlighting that a cell can die via a number of differing pathways. Apoptosis is characterised by a number of characteristic morphological changes in the structure of the cell, together with a number of enzyme‐dependent biochemical processes. The result being the clearance of cells from the body, with minimal damage to surrounding tissues. Necrosis, however, is generally characterised to be the uncontrolled death of the cell, usually following a severe insult, resulting in spillage of the contents of the cell into surrounding tissues and subsequent damage thereof. Failure of apoptosis and the resultant accumulation of damaged cells in the body can result in various forms of cancer. An understanding of the pathways is therefore important in developing efficient chemotherapeutics. It has recently become clear that there exists a number of subtypes of apoptosis and that there is an overlap between apoptosis, necrosis and autophagy. The goal of this review is to provide a general overview of the current knowledge relating to the various forms of cell death, including apoptosis, necrosis, oncosis, pyroptosis and autophagy. This will provide researchers with a summary of the major forms of cell death and allow them to compare and contrast between them.

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“…Necroptosis is a form of programmed cell death that exhibits necrosis-like morphological features. Necroptosis is associated with the permeabilization of cellular membranes, the release of cellular and organelle contents into the extracellular medium, and inflammation [17,[30][31][32]. The most defined molecular pathway of necroptosis is mediated by TNF-α receptor through receptor-interacting serine/threonine-protein kinase 1 and 3 (RIPK1 and RIPK3) and the pseudokinase mixed-lineage kinase domain-like (MLKL).…”

Section: Aging Cochleae Exhibit Necroptosis and An Inflammatory Responsementioning

confidence: 99%

Mitochondrial Damage and Necroptosis in Aging Cochlea

Lyu

Kim

Park

et al. 2020

IJMS

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Age-related hearing loss (ARHL) is an irreversible, progressive neurodegenerative disorder and is presently untreatable. Previous studies using animal models have suggested mitochondrial damage and programmed cell death to be involved with ARHL. Thus, we further investigated the pathophysiologic role of mitochondria and necroptosis in aged C57BL/6J male mice. Aged mice (20 months old) exhibited a significant loss of hearing, number of hair cells, neuronal fibers, and synaptic ribbons compared to young mice. Ultrastructural analysis of aged cochleae revealed damaged mitochondria with absent or disorganized cristae. Aged mice also showed significant decrease in cochlear blood flow, and exhibited increase in gene expression of proinflammatory cytokines (IL-1β, IL-6, and TNF-α), receptor-interacting serine/threonine-protein kinase 1 and 3 (RIPK1 and RIPK3) and the pseudokinase mixed-lineage kinase domain-like (MLKL). Immunofluorescence (IF) assays of cytochrome C oxidase I (COX1) confirmed mitochondrial dysfunction in aged cochleae, which correlated with the degree of mitochondrial morphological damage. IF assays also revealed localization and increased expression of RIPK3 in sensorineural tissues that underwent significant necroptosis (inner and outer hair cells and stria vascularis). Together, our data shows that the aging cochlea exhibits damaged mitochondria, enhanced synthesis of proinflammatory cytokines, and provides new evidence of necroptosis in the aging cochlea in in vivo.

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Mechanism and disease implications of necroptosis and neuronal inflammation

Cited by 17 publications

References 16 publications

Melatonin Suppresses Microglial Necroptosis by Regulating Deubiquitinating Enzyme A20 After Intracerebral Hemorrhage

Melatonin Suppresses Microglial Necroptosis by Regulating Deubiquitinating Enzyme A20 After Intracerebral Hemorrhage

Cell death: a review of the major forms of apoptosis, necrosis and autophagy

Mitochondrial Damage and Necroptosis in Aging Cochlea

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