MLKL regulates Cx43 ubiquitinational degradation and mediates neuronal necroptosis in ipsilateral thalamus after focal cortical infarction

GBD 2019 Stroke Collaborators. Global, regional, and national burden of Stroke and its risk factors, 1990–2019: a systematic analysis for the global burden of Disease Study 2019. Lancet Neurol. 2021;20(10):795–820.

Article  Google Scholar 

Forno LS. Reaction of the substantia nigra to massive basal ganglia infarction. Acta Neuropathol. 1983;62(1–2):96–102.

Article  CAS  PubMed  Google Scholar 

Jin J, Tang Y, Li K, Zuo X, Zhan L, Sun W, Xu E. Bone marrow stromal cells alleviate secondary damage in the Substantia Nigra after focal cerebral infarction in rats. Front Cell Neurosci. 2019;13:338.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Zhang J, Zhang Y, Xing S, Liang Z, Zeng J. Secondary neurodegeneration in remote regions after focal cerebral infarction: a new target for Stroke management? Stroke. 2012;43(6):1700–5.

Article  PubMed  Google Scholar 

Springer J, Schust S, Peske K, Tschirner A, Rex A, Engel O, Scherbakov N, Meisel A, von Haehling S, Boschmann M, Anker SD, Dirnagl U, Doehner W. Catabolic signaling and muscle wasting after acute ischemic Stroke in mice: indication for a stroke-specific Sarcopenia. Stroke. 2014;45(12):3675–83.

Article  CAS  PubMed  Google Scholar 

Dang G, Chen X, Chen Y, Zhao Y, Ouyang F, Zeng J. Dynamic secondary degeneration in the spinal cord and ventral root after a focal cerebral infarction among hypertensive rats. Sci Rep. 2016;6:22655.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Ouyang F, Jiang Z, Chen X, Chen Y, Wei J, Xing S, Zhang J, Fan Y, Zeng J. Is cerebral Amyloid-β deposition related to post-stroke cognitive impairment? Transl Stroke Res. 2021;12(6):946–57.

Article  CAS  PubMed  Google Scholar 

Zuo X, Hou Q, Jin J, Chen X, Zhan L, Tang Y, Shi Z, Sun W, Xu E. Inhibition of cathepsins B induces Neuroprotection Against secondary degeneration in Ipsilateral Substantia Nigra after Focal Cortical Infarction in adult male rats. Front Aging Neurosci. 2018;10:125.

Article  PubMed  PubMed Central  Google Scholar 

Rodriguez-Grande B, Blackabey V, Gittens B, Pinteaux E, Denes A. Loss of substance P and inflammation precede delayed neurodegeneration in the substantia nigra after cerebral ischemia. Brain Behav Immun. 2013;29:51–61.

Article  CAS  PubMed  Google Scholar 

Kirton A, Shroff M, Visvanathan T, deVeber G. Quantified corticospinal tract diffusion restriction predicts neonatal Stroke outcome. Stroke. 2007;38(3):974–80.

Article  PubMed  Google Scholar 

Domi T, deVeber G, Shroff M, Kouzmitcheva E, MacGregor DL, Kirton A. Corticospinal tract pre-wallerian degeneration: a novel outcome predictor for pediatric Stroke on acute MRI. Stroke. 2009;40(3):780–7.

Article  PubMed  Google Scholar 

DeVetten G, Coutts SB, Hill MD, Goyal M, Eesa M, O’Brien B, Demchuk AM, Kirton A. Acute corticospinal tract Wallerian degeneration is associated with stroke outcome. Stroke. 2010;41(4):751–6. & MONITOR and VISION study groups

Baron JC, Yamauchi H, Fujioka M, Endres M. Selective neuronal loss in ischemic Stroke and Cerebrovascular Disease. J Cereb Blood Flow Metab. 2014;34(1):2–18.

Article  PubMed  Google Scholar 

Zuo X, et al. Inhibition of cathepsin B alleviates secondary degeneration in ipsilateral thalamus after focal cerebral infarction in adult rats. J Neuropathol Exp Neurol. 2016;75(9):816–26.

Article  CAS  PubMed  Google Scholar 

Zuo X, Hou Q, Jin J, Zhan L, Li X, Sun W, Lin K, Xu E. Attenuation of secondary damage and Aβ deposits in the ipsilateral thalamus of dMCAO rats through reduction of cathepsin B by bis(propyl)-cognitin, a multifunctional dimer. Neuropharmacology. 2016;162:107786.

Article  Google Scholar 

Wang F, Liang Z, Hou Q, Xing S, Ling L, He M, Pei Z, Zeng J. Nogo-A is involved in secondary axonal degeneration of thalamus in hypertensive rats with focal cortical infarction. Neurosci Lett. 2007;417(3):255–60.

Article  CAS  PubMed  Google Scholar 

Zhang Y, Xing S, Zhang J, Li J, Li C, Pei Z, Zeng J. Reduction of β-amyloid deposits by γ-secretase inhibitor is associated with the attenuation of secondary damage in the ipsilateral thalamus and sensory functional improvement after focal cortical infarction in hypertensive rats. J Cereb Blood Flow Metab. 2011;31(2):572–9.

Article  CAS  PubMed  Google Scholar 

Xing S, Zhang Y, Li J, Zhang J, Li Y, Dang C, Li C, Fan Y, Yu J, Pei Z, Zeng J. Beclin 1 knockdown inhibits autophagic activation and prevents the secondary neurodegenerative damage in the ipsilateral thalamus following focal cerebral infarction. Autophagy. 2012;8(1):63–76.

Article  CAS  PubMed  Google Scholar 

Xing S, Zhang J, Dang C, Liu G, Zhang Y, Li J, Fan Y, Pei Z, Zeng J. Cerebrolysin reduces amyloid-β deposits, apoptosis and autophagy in the thalamus and improves functional recovery after cortical infarction. J Neurol Sci. 2014;337(1–2):104–11.

Article  CAS  PubMed  Google Scholar 

Chen Y, Veenman L, Singh S, Ouyang F, Liang J, Huang W, Marek I, Zeng J, Gavish M. 2-Cl-MGV-1 ameliorates apoptosis in the Thalamus and Hippocampus and cognitive deficits after cortical infarct in rats. Stroke. 2017;48(12):3366–74.

Article  CAS  PubMed  Google Scholar 

Block F, Dihné M, Loos M. Inflammation in areas of remote changes following focal brain lesion. Prog Neurobiol. 2005;75(5):342–65.

Article  CAS  PubMed  Google Scholar 

He M, Xing S, Yang B, Zhao L, Hua H, Liang Z, Zhou W, Zeng J, Pei Z. Ebselen attenuates oxidative DNA damage and enhances its repair activity in the thalamus after focal cortical infarction in hypertensive rats. Brain Res. 2007;1181:83–92.

Article  CAS  PubMed  Google Scholar 

Zhao J, Jitkaew S, Cai Z, Choksi S, Li Q, Luo J, Liu ZG. Mixed lineage kinase domain-like is a key receptor interacting protein 3 downstream component of TNF-induced necrosis. Proc Natl Acad Sci. 2012;109(14):5322–7.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Murphy JM, Czabotar PE, Hildebrand JM, Lucet IS, Zhang JG, Alvarez-Diaz S, Lewis R, Lalaoui N, Metcalf D, Webb AI, Young SN, Varghese LN, Tannahill GM, Hatchell EC, Majewski IJ, Okamoto T, Dobson RC, Hilton DJ, Babon JJ, Nicola NA, Strasser A, Silke J, Alexander WS. The pseudokinase MLKL mediates necroptosis via a molecular switch mechanism. Immunity. 2013;39(3):443–53.

Article  CAS  PubMed  Google Scholar 

Wang H, Sun L, Su L, Rizo J, Liu L, Wang LF, Wang FS, Wang X. Mixed lineage kinase domain-like protein MLKL causes necrotic membrane disruption upon phosphorylation by RIP3. Mol Cell. 2014;54(1):133–46.

Article  CAS  PubMed  Google Scholar 

Deng XX, Li SS, Sun FY. Necrostatin-1 prevents necroptosis in brains after ischemic Stroke via inhibition of RIPK1-Mediated RIPK3/MLKL signaling. Aging Dis. 2019;10(4):807–17.

Article  PubMed  PubMed Central  Google Scholar 

Zhan Q, Jeon J, Li Y, Huang Y, Xiong J, Wang Q, Xu TL, Li Y, Ji FH, Du G, Zhu MX. (2022) CAMK2/CaMKII activates MLKL in short-term Starvation to facilitate autophagic flux. Autophagy 1–19.

Zhu YM, Lin L, Wei C, Guo Y, Qin Y, Li ZS, Kent TA, McCoy CE, Wang ZX, Ni Y, Zhou XY, Zhang HL. The key regulator of necroptosis, RIP1 kinase, contributes to the formation of astrogliosis and glial scar in ischemic Stroke. Translational Stroke Research. 2021;12(6):991–1017.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Hildebrand JM, Tanzer MC, Lucet IS, Young SN, Spall SK, Sharma P, Pierotti C, Garnier JM, Dobson RC, Webb AI, Tripaydonis A, Babon JJ, Mulcair MD, Scanlon MJ, Alexander WS, Wilks AF, Czabotar PE, Lessene G, Murphy JM, Silke J. Activation of the pseudokinase MLKL unleashes the four-helix bundle domain to induce membrane localization and necroptotic cell death. Proc Natl Acad Sci. 2014;111(42):15072–7.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Chen X, Li W, Ren J, Huang D, He WT, Song Y, Yang C, Li W, Zheng X, Chen P, Han J. Translocation of mixed lineage kinase domain-like protein to plasma membrane leads to necrotic cell death. Cell Res. 2014;24(1):105–21.

Article  CAS  PubMed  Google Scholar 

Dondelinger Y, Declercq W, Montessuit S, Roelandt R, Goncalves A, Bruggeman I, Hulpiau P, Weber K, Sehon CA, Marquis RW, Bertin J, Gough PJ, Savvides S, Martinou JC, Bertrand MJ, Vandenabeele P. MLKL compromises plasma membrane integrity by binding to phosphatidylinositol phosphates. Cell Rep. 2014;7(4):971–81.

Article  CAS  PubMed  Google Scholar 

Zhang Y, Liu J, Yu D, Zhu X, Liu X, Liao J, Li S, Wang H. The MLKL kinase-like domain dimerization is an indispensable step of mammalian MLKL activation in necroptosis signaling. Cell Death Dis. 2021;12(7):638.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Cai Z, Jitkaew S, Zhao J, Chiang HC, Choksi S, Liu J, Ward Y, Wu LG, Liu ZG. Plasma membrane translocation of trimerized MLKL protein is required for TNF-induced necroptosis. Nat Cell Biol. 2014;16(1):55–65.

Article  CAS  PubMed  Google Scholar 

Gong YN, Guy C, Olauson H, Becker JU, Yang M, Fitzgerald P, Linkermann A, Green DR. ESCRT-III acts downstream of MLKL to regulate necroptotic cell death and its consequences. Cell. 2017;169(2):286–300e16.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Zhan L, Lu X, Xu W, Sun W, Xu E. Inhibition of MLKL-dependent necroptosis via downregulating interleukin-1R1 contributes to neuroprotection of hypoxic preconditioning in transient global cerebral ischemic rats. J Neuroinflammation. 2021;18(1):97.

Article  CAS  PubMed 

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