Ask about this productRelated genes to: MLKL antibody
- Gene:
- MLKL NIH gene
- Name:
- mixed lineage kinase domain like pseudokinase
- Previous symbol:
- -
- Synonyms:
- FLJ34389
- Chromosome:
- 16q22.3
- Locus Type:
- gene with protein product
- Date approved:
- 2005-02-10
- Date modifiied:
- 2016-10-19
Related products to: MLKL antibody
Related articles to: MLKL antibody
- Microglia are the resident immune cells of the brain; they respond rapidly to inflammatory stimuli and contribute to the progression of neurodegenerative diseases. Receptor-interacting protein kinase 3 (RIPK3) is known to mediate pro-inflammatory signaling and necroptosis, a form of regulated necrotic cell death. However, the role of RIPK3 in microglial activation remains unclear. This study aimed to investigate the role of RIPK3 in both in vitro and in vivo models of neuroinflammation and necroptosis using a selective RIPK3 inhibitor, GSK872. In lipopolysaccharide (LPS)-injected mice, GSK872 attenuated microglial activation, decreased the expression of pro-inflammatory mediators, and reduced the phosphorylation of RIPK3 and mixed lineage kinase domain-like protein (MLKL). In BV2 microglial cells, GSK872 suppressed the production of inflammatory mediators under both inflammatory and necroptotic conditions induced by LPS or LPS/Z-VAD. In particular, GSK872 reduced necroptosis-associated cell death and the release of HMGB1 and IL-1β in LPS/Z-VAD-treated cells. Detailed mechanistic studies revealed that GSK872 inhibits the c-Jun N-terminal kinase (JNK) pathway, while pharmacological inhibition of JNK using SP600125 recapitulates the effects of GSK872 on inflammatory and necroptotic markers. These results indicate that JNK plays a critical role in mediating the effects of GSK872. Notably, IL-1β released during necroptosis appears to contribute modestly to the phosphorylation of JNK and MLKL, indicating a potential feedback mechanism that reinforces necroptotic signaling. Our findings provide compelling evidence that the inhibition of RIPK3 by GSK872 alleviates neuroinflammatory responses and necroptotic cell death by modulating JNK signaling in activated microglia, offering a promising therapeutic strategy for neurodegenerative diseases. - Source: PubMed
Publication date: 2026/04/30
Park Jin-SunKim Do-YeonKim Seong-EunHyun Jin-WonKim Hee-Sun - Sepsis-induced acute lung injury (ALI) is driven by macrophage-mediated inflammation and PANoptosis. Eucommia ulmoides Oliv. (Du Zhong, DZ) contains anti-inflammatory phytochemicals, but crude extracts show poor solubility, rapid clearance and a narrow therapeutic window. We therefore tested whether a nanoliposomal DZ formulation (Nano-LP-DZ) could improve efficacy in experimental sepsis-induced ALI. - Source: PubMed
Publication date: 2026/04/29
Deng MingtaoTong ZherenLi XinChen SiqiWu JianDai JiahengXu JingqingLi MinCao LiuWeng XinhuiWang JingweiZeng LongGong YuanqiGao YiShang XiulingDai Wei - Vibrio vulnificus, a gram-negative bacterium, commonly infects humans via contaminated seafood or wounds and can cause severe sepsis. The multifunctional autoprocessing repeat-in-toxin (MARTX) is one of the most crucial virulence factors in V. vulnificus, associated with host pathogenesis. V. vulnificus MARTX induces serious cell damage, leading to subsequent cell death. However, the specific modalities of cell death are diverse and not fully understood. - Source: PubMed
Publication date: 2026/04/20
Lo Horng-RenHsieh Chia-MingChen Chun-YaHuang Shiao-PingWang Yu-TingHuang Yu-TsenBui Ngoc-NiemChiu Cheng-HsunLai Chih-Ho - Aging is the major risk factor for several chronic conditions, including cognitive decline and dementia. It is accompanied by profound immune alterations characterized by a progressive decline in immune competence, a process known as immunosenescence. The resulting dysregulation of immune function leads to the overproduction of proinflammatory cytokines and fuels a persistent, low-grade inflammatory state termed inflammaging. This chronic inflammation contributes to dysfunction across the central and peripheral nervous systems, promoting neuronal damage and accelerating neurodegenerative processes such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and other age-related cognitive disorders. Within this framework, prolonged activation of inflammatory pathways can trigger regulated forms of cell death. Among these, necroptosis has recently emerged as a potential mediator linking inflammaging to neurodegeneration. Its core molecular effectors, including the receptor-interacting protein kinases RIPK1 and RIPK3 and the mixed-lineage kinase domain-like protein (MLKL), are increasingly expressed in aged neural tissues, promoting the release of damage-associated molecular patterns (DAMPs) that amplify glial activation, oxidative stress, and blood-brain barrier disruption. Growing evidence suggests that necroptotic signaling may be upregulated in the aging brain and in neurodegenerative disorders, where it could contribute to neuronal loss and cognitive impairment. This review discusses the potential role of necroptosis in the continuum between inflammation and neurodegeneration, highlighting emerging diagnostic and therapeutic perspectives. Epigenetic and circulating biomarkers, such as phosphorylated MLKL and specific microRNAs, may support early detection, while pharmacological and nutraceutical strategies targeting necroptosis show promising neuroprotective effects in preclinical studies. - Source: PubMed
Publication date: 2026/04/28
Biscetti LeonardoGambuzza Maria ElsaPrinciotto MariaSabbatinelli JacopoOlivieri FabiolaFiorillo MarcoChinigò ChiaraMuglia LuciaCozza AnnalisaBeccacece AlessiaGembillo GuidoBruschetta GiuseppeVillalta Savedra EdlinLattanzio FabriziaCorsonello AndreaSoraci Luca - Chronic kidney disease (CKD) is a prevalent global health concern with a high worldwide prevalence rate. It is defined by a steady deterioration in renal function, which causes toxins and metabolic waste to build up and cause systemic problems and multi-organ failure. The development and progression of CKD are influenced by a number of pathogenic factors, such as diabetes mellitus, hypertension, glomerulonephritis, and exposure to nephrotoxic chemicals. However, the precise underlying mechanisms remain incompletely understood. Necroptosis, a well-studied form of regulated cell death, is primarily mediated by the receptor-interacting protein kinase 1 (RIPK1) and receptor-interacting protein kinase 3 (RIPK3) signaling complex. Understanding necroptosis provides new avenues for therapeutic modulation of cillnehronic kidney disease, linking regulated cell death to fibrosis and inflammation. RIPK3 expression is upregulated up to five-fold in experimental CKD models, underscoring its pathogenic significance. The definition, key molecular mechanisms, and most current advancements in pharmacological research pertaining to necroptosis are all comprehensively summarized in this article. This review provides mechanistic insights into necroptosis in CKD and highlights therapeutic targets for future translational research. - Source: PubMed
Publication date: 2026/04/27
Lu JiaweiWang YingCheng YalinZhou ShuyuanLiao YunqiangZeng JiqiangZhang ShanrongTang Yang