Results 61 to 70 of about 13,017 (220)

Ubiquitylation of MLKL at lysine 219 positively regulates necroptosis-induced tissue injury and pathogen clearance [PDF]

, 2021
Necroptosis is a lytic, inflammatory form of cell death that not only contributes to pathogen clearance but can also lead to disease pathogenesis. Necroptosis is triggered by RIPK3-mediated phosphorylation of MLKL, which is thought to initiate MLKL ...
Tenev, T, Yu, L, Beal, AM, Liang, LY, Liccardi, G, John, SW, Fitzgibbon, C, Geddes, B, Garcia, LR, Ward, G, Fernando, W, Smyth, T, Kueh, A, Pardo, M, Young, SN, Murphy, JM, Aurelia Ball, K, Guppy, N, Bertin, J, Upton, JW, Gazinska, P, Roxanis, I, Annibaldi, A, Kim, H, Lucet, IS, Sims, M, Liang, L-Y, Newman, R, Haich, RO, Choudhary, JS, Meier, P   +30 more
core   +1 more source

Thymosin Alpha‐1 Provides Direct Neuroprotection by Engaging the Orexin Receptor HCRTR1 to Suppress Neuronal Necroptosis

Advanced Science, EarlyView.
In this study, we unveil a thymus‐brain endocrine axis wherein Tα1 engages HCRTR1 to inhibit RIPK3‐mediated necroptosis. This study nominates the Tal‐HCRTR1‐RIPK3 axis as a potent and clinically translatable therapeutic target for stroke and neurodegeneration.
Xinmei Kang, Shisi Wang, Liubin Zhang, Mengyan Hu, Xiaotao Su, Yuxin Liu, Qin Qin, Haotong Yi, Liling Yuan, Wei Cai, Lei Wei, Zhengqi Lu   +11 more
wiley   +1 more source

Viral MLKL Homologs Subvert Necroptotic Cell Death by Sequestering Cellular RIPK3

Cell Reports, 2019
Summary: Necroptotic cell death has been implicated in many human pathologies and is thought to have evolved as an innate immunity mechanism. The pathway relies on two key effectors: the kinase receptor-interacting protein kinase 3 (RIPK3) and the ...
Emma J. Petrie, Jarrod J. Sandow, Wil I.L. Lehmann, Lung-Yu Liang, Diane Coursier, Samuel N. Young, Wilhelmus J.A. Kersten, Cheree Fitzgibbon, André L. Samson, Annette V. Jacobsen, Kym N. Lowes, Amanda E. Au, Hélène Jousset Sabroux, Najoua Lalaoui, Andrew I. Webb, Guillaume Lessene, Gerard Manning, Isabelle S. Lucet, James M. Murphy   +18 more
doaj   +1 more source

Skp2-mediated MLKL degradation confers cisplatin-resistant in non-small cell lung cancer cells

Communications Biology, 2023
Non-small cell lung cancer (NSCLC) is the most prevalent type of cancer and the leading cause of cancer-related death. Chemotherapeutic resistance is a major obstacle in treating NSCLC patients.
Huiling Zhou, Li Zhou, Qing Guan, Xuyang Hou, Cong Wang, Lijun Liu, Jian Wang, Xinfang Yu, Wei Li, Haidan Liu   +9 more
doaj   +1 more source

Nuclear translocation of MLKL enhances necroptosis by a RIP1/RIP3-independent mechanism in H9c2 cardiomyoblasts

Journal of Pharmacological Sciences, 2023
Accumulating evidence suggests that necroptosis of cardiomyocytes contributes to cardiovascular diseases. Lethal disruption of the plasma membrane in necroptosis is induced by oligomers of mixed lineage kinase domain-like (MLKL) that is translocated to ...
Shoya Ino, Toshiyuki Yano, Atsushi Kuno, Masaya Tanno, Hidemichi Kouzu, Tatsuya Sato, Tomohisa Yamashita, Wataru Ohwada, Arata Osanami, Toshifumi Ogawa, Yuki Toda, Masaki Shimizu, Tetsuji Miura   +12 more
doaj   +1 more source

Lactate‐Driven Restriction of Mitochondrial Permeability Transition Promotes Resistance to Chemo‐Immunotherapy by Suppressing Tumor PANoptosis

Advanced Science, EarlyView.
Tumor‐derived lactate establishes a metabolic lock that drives chemo‐immunotherapy resistance by suppressing PANoptosis. Mechanistically, KAT8 lactylates the mitochondrial translocator ANT2, which recruits PGAM5 to dephosphorylate CypD. This cascade restricts mitochondrial permeability transition pore opening, preventing pro‐inflammatory mtDNA leakage.
Sen Zhong, Wenlong Chen, Fanglong Liu, Shengyi Zhou, Bolin Yu, Yuying Wang, Xiqian Zhou, Xuehui Wang, Diya Liu, Zhuoyu Zhang, Xinran Wang, Mounia Lalouly, Yiwen Li, Zhefei Du, Tao Yan, Zhihui Xiao, Zhou Zhou, Huanhuan Zhu, Fengyuan Qian, Bowen Zheng, Lin Fang   +20 more
wiley   +1 more source

Necroptosis in bacterial infections

Frontiers in Immunology
Necroptosis, a recently discovered form of cell-programmed death that is distinct from apoptosis, has been confirmed to play a significant role in the pathogenesis of bacterial infections in various animal models. Necroptosis is advantageous to the host,
Xing Yu, Jin Yuan, Linxi Shi, Shuying Dai, Lei Yue, Min Yan   +5 more
doaj   +1 more source

Neuron‐Targeted Exosomal Delivery of siRNA Against RIPK3 Slows Neurodegenerative Progression in Alzheimer's Disease

Advanced Science, EarlyView.
Engineered exosomal siRNA delivery platform enables systemic, neuron‐targeted RNA transport across the blood–brain barrier. Surface functionalization with rabies virus glycoprotein‐derived peptide facilitates receptor‐mediated transcytosis, achieving efficient cytosolic delivery and robust gene silencing. Targeting RIPK3 suppresses necroptosis, reduces
Chi Zhang, Jiaqi Zhang, Yuzhi Wang, Yaodong Wang, Peng Lin, Yanling Wang, Zixuan Tang, Jintai Yu, Qin Zhou, Feiyun Cui   +9 more
wiley   +1 more source

The pseudokinase MLKL contributes to host defense against Streptococcus pluranimalium infection by mediating NLRP3 inflammasome activation and extracellular trap formation

Virulence, 2023
Host innate immunity plays a pivotal role in the early detection and neutralization of invading pathogens. Here, we show that pseudokinase mixed lineage kinase-like protein (MLKL) is required for host defence against Streptococcus pluranimalium infection
Yu-Xin Lei, Yang Liu, Li-Hua Xing, Yu-Jing Wu, Xue-Yin Wang, Fan-Hua Meng, Ya-Nan Lou, Zhao-Guo Ma, Lin Yuan, Shui-Xing Yu   +9 more
doaj   +1 more source

Aberrant GRP78 Phase Transition Sustains Endothelial IRE1α Signaling and Drives Blood–Brain Barrier Failure in Cerebral Amyloid Angiopathy

Advanced Science, EarlyView.
Vascular Aβ40 corrupts GRP78 phase behavior in brain endothelial cells, sustaining IRE1α–TRAF2–JNK signaling and driving apoptosis, tight junction loss, and blood–brain barrier failure in cerebral amyloid angiopathy. Pharmacological IRE1α inhibition restores vascular integrity, reduces leakage, and improves functional outcomes, revealing a targetable ...
Honglin Zheng, Qiang Li, Haiyang Luo, Yapei Yuan, Na Zhang, Yongting Lu, Suying Duan, Jieshi Zhong, Hang Zhang, Chenyang Liu, Yaochong Zhang, Wenzhuo Zhao, Yaxuan Song, Tuo Wang, Si Yan, Yapeng Li, Han Liu, Yuan Gao, Zongping Xia, Yuming Xu   +19 more
wiley   +1 more source