Necroptosis in development and diseases

Shan, Bing; Pan, Heling; Najafov, Ayaz; Yuan, Junying

doi:10.1101/gad.312561.118

Cited by 267 publications

(200 citation statements)

References 139 publications

Supporting

Mentioning

194

Contrasting

Unclassified

Order By: Relevance

“…Necroptosis is a programmed cell death mechanism currently associated with cell death in several pathological conditions such as ischemia-reperfusion injury in the heart, liver injury, viral infection, cancer and neurodegeneration (Shan et al, 2003;Tonnus and Linkermann, 2017). Necroptosis can be initiated by a variety of stimuli often related to inflammation (Wallach et al, 2016), including TNF-α, Fas, TRAIL, interferons and activation of TLR by LPS, dsRNA, DNA damage, viral infection, among others (review in Grootjans et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

The necroptosis machinery mediates axonal degeneration in a model of Parkinson disease

Oñate

Catenaccio

Salvadores

et al. 2019

Preprint

View full text Add to dashboard Cite

Parkinson's disease (PD) is the second most common neurodegenerative condition, characterized by motor impairment due to the progressive degeneration of dopaminergic neurons in the substantia nigra and depletion of dopamine release in the striatum.Accumulating evidence suggest that degeneration of axons is an early event in the disease, involving destruction programs that are independent of the survival of the cell soma. Necroptosis, a programmed cell death process, is emerging as a mediator of neuronal loss in models of neurodegenerative diseases. Here, we demonstrate activation of necroptosis in postmortem brain tissue from PD patients and in a toxin-based mouse model of the disease. Inhibition of key components of the necroptotic pathway resulted in a significant delay of 6-hydroxydopamine dependent axonal degeneration of dopaminergic and cortical neurons in vitro. Genetic ablation of necroptosis mediators MLKL and RIPK3, as well as pharmacological inhibition of RIPK1 in vivo, decreased dopaminergic neuron degeneration, improving motor performance. Together, these findings suggest that axonal degeneration in PD is mediated by the necroptosis machinery, a process here referred to as necroaxoptosis, a druggable pathway to target dopaminergic neuronal loss.

show abstract

Section: Introductionmentioning

confidence: 99%

The necroptosis machinery mediates axonal degeneration in a model of Parkinson disease

Oñate

Catenaccio

Salvadores

et al. 2019

Preprint

View full text Add to dashboard Cite

show abstract

“…However, previous evidence has not definitively demonstrated a critical role for necroptosis in DSS-induced colitis. According to published data, the RIPK1-RIPK3-MLKL signaling pathway is the critical regulatory mechanism for necroptosis (Shan et al, 2018). Nec-1, a RIPK1 inhibitor, suppresses DSS-induced colitis, but it's also an inhibitor of indoleamine 2,3-dioxygenase, which contributes to development of colitis (Harrington et al, 2008;Liu et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

Inhibition of HtrA2 alleviated colitis by preventing necroptosis of intestinal epithelial cells

Yan

Zhang

et al. 2018

Preprint

View full text Add to dashboard Cite

Necroptosis of intestinal epithelial cells has been indicated to play an important role in the pathogenesis of inflammatory bowel disease (IBD). The identification of dysregulated proteins that can regulate necroptosis in dextran sulfate sodium (DSS)-induced colitis is the key to the rational design of therapeutic strategies for colitis. Through Tandem Mass Tag (TMT)-based quantitative proteomics, HtrA2 was found to be downregulated in the colon of DSS-treated mice. UCF-101, a specific serine protease inhibitor of HtrA2, significantly alleviated DSS-induced colitis as indicated by prevention of body weight loss and decreased mortality. UCF-101 decreased DSS-induced colonic inflammation, prevented intestinal barrier function loss and inhibited necroptosis of intestinal epithelial cells. In vitro, UCF-101 or silencing of HtrA2 decreased necroptosis of HT-29 and L929 cells. UCF-101 decreased phosphorylation of RIPK1 and subsequent phosphorylation of RIPK3 and MLKL during necroptosis. HtrA2 directly interacted with RIPK1 and promoted its degradation during a specific time phase of necroptosis. Our findings highlight the importance of HtrA2 in regulating colitis by modulation of necroptosis and suggest HtrA2 as an attractive target for anti-colitis treatment.

show abstract

“…Although the subsequent molecular cascades or cellular interactions after necroptosis of AEII cells have yet to be determined, our study suggests that blocking necroptosis in AEII cells should suppress the very early events that lead to pulmonary fibrosis in IPF patients. The activation of RIPK1 leads to cell death through the formation of a RIPK1-TRADD-FADD-caspase-8 complex (Shan et al, 2018;Yuan et al, 2019). This complex triggers caspase activation and causes RIPK1-dependent apoptosis.…”

Section: Influenza Virus Infection Accelerated Pulmonary Fibrosis Inmentioning

confidence: 99%

A homozygous SFTPA1 mutation drives necroptosis of type II alveolar epithelial cells in patients with idiopathic pulmonary fibrosis

Takezaki

Tsukumo

Setoguchi

et al. 2019

Journal of Experimental Medicine

View full text Add to dashboard Cite

Idiopathic pulmonary fibrosis (IPF) is a fatal disease characterized by scattered fibrotic lesions in the lungs. The pathogenesis and genetic basis of IPF remain poorly understood. Here, we show that a homozygous missense mutation in SFTPA1 caused IPF in a consanguineous Japanese family. The mutation in SFTPA1 disturbed the secretion of SFTPA1 protein. Sftpa1 knock-in (Sftpa1-KI) mice that harbored the same mutation as patients spontaneously developed pulmonary fibrosis that was accelerated by influenza virus infection. Sftpa1-KI mice showed increased necroptosis of alveolar epithelial type II (AEII) cells with phosphorylation of IRE1α leading to JNK-mediated up-regulation of Ripk3. The inhibition of JNK ameliorated pulmonary fibrosis in Sftpa1-KI mice, and overexpression of Ripk3 in Sftpa1-KI mice treated with a JNK inhibitor worsened pulmonary fibrosis. These findings provide new insight into the mechanisms of IPF in which a mutation in SFTPA1 promotes necroptosis of AEII cells through JNK-mediated up-regulation of Ripk3, highlighting the necroptosis pathway as a therapeutic target for IPF.

show abstract

Necroptosis in development and diseases

Cited by 267 publications

References 139 publications

The necroptosis machinery mediates axonal degeneration in a model of Parkinson disease

The necroptosis machinery mediates axonal degeneration in a model of Parkinson disease

Inhibition of HtrA2 alleviated colitis by preventing necroptosis of intestinal epithelial cells

A homozygous SFTPA1 mutation drives necroptosis of type II alveolar epithelial cells in patients with idiopathic pulmonary fibrosis

Contact Info

Product

Resources

About