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Review Article

The c-Jun N-terminal kinase signaling pathway in epilepsy: activation, regulation, and therapeutics

ORCID Icon, , ORCID Icon, ORCID Icon & ORCID Icon
Pages 492-498 | Received 14 Aug 2018, Accepted 25 Feb 2019, Published online: 30 Apr 2019

References

  • Trinka E, Kwan P, Lee B, et al. Epilepsy in Asia: disease burden, management barriers, and challenges. Epilepsia. 2018. DOI:10.1111/epi.14458
  • Pearson-Smith JN, Patel M. Metabolic dysfunction and oxidative stress in epilepsy. Int J Mol Sci. 2017;18:2365.
  • Guo XX, An S, Yang Y, et al. Emerging role of the jun n-terminal kinase interactome in human health. Cell Biol Int. 2018;42:756–768.
  • Davis RJ. Signal transduction by the JNK group of map kinases. Cell. 2000;103:239–252.
  • Sabio G, Davis RJ. TNF and map kinase signalling pathways. Semin Immunol. 2014;26:237–245.
  • Ge HX, Zou FM, Li Y, et al. JNK pathway in osteoarthritis: pathological and therapeutic aspects. J Recept Signal Transduct Res. 2017;37:431–436.
  • Solinas G, Becattini B. JNK at the crossroad of obesity, insulin resistance, and cell stress response. Mol Metab. 2017;6:174–184.
  • Tai TY, Warner LN, Jones TD, et al. Antiepileptic action of c-jun n-terminal kinase (JNK) inhibition in an animal model of temporal lobe epilepsy. Neuroscience. 2017;349:35–47.
  • de Lemos L, Junyent F, Camins A, et al. Neuroprotective effects of the absence of jnk1 or jnk3 isoforms on kainic acid-induced temporal lobe epilepsy-like symptoms. Mol Neurobiol. 2018;55:4437–4452.
  • Boehm R, Concepcion F, Poolos N. C-jun n-terminal kinase signaling in chronic epilepsy. J Investig Med. 2016;64:187.
  • Kariminejad R, Lind-Thomsen A, Tumer Z, et al. High frequency of rare copy number variants affecting functionally related genes in patients with structural brain malformations. Hum Mutat. 2011;32:1427–1435.
  • Shinoda S, Skradski SL, Araki T, et al. Formation of a tumour necrosis factor receptor 1 molecular scaffolding complex and activation of apoptosis signal-regulating kinase 1 during seizure-induced neuronal death. Eur J Neurosci. 2003;17:2065–2076.
  • Hayakawa R, Hayakawa T, Takeda K, et al. Therapeutic targets in the ask1-dependent stress signaling pathways. Proc Jpn Acad Ser B Phys Biol Sci. 2012;88:434–453.
  • Nishida T, Hattori K, Watanabe K. The regulatory and signaling mechanisms of the ask family. Adv Biol Regul. 2017;66:2–22.
  • Iurlaro R, Munoz-Pinedo C. Cell death induced by endoplasmic reticulum stress. Febs J. 2016;283:2640–2652.
  • Liu G, Guo H, Guo C, et al. Involvement of IRE1α signaling in the hippocampus in patients with mesial temporal lobe epilepsy. Brain Res Bull. 2011;84:94–102.
  • Pal S, Limbrick DD, Jr., Rafiq A, et al. Induction of spontaneous recurrent epileptiform discharges causes long-term changes in intracellular calcium homeostatic mechanisms. Cell Calcium. 2000;28:181–193.
  • Liao ET, Lin YW, Huang CP, et al. Electric stimulation of ear reduces the effect of toll-like receptor 4 signaling pathway on kainic acid-induced epileptic seizures in rats. Biomed Res Int. 2018;2018:1.
  • Mou J, Liu X, Pei D. Overexpression of c-terminal fragment of glutamate receptor 6 prevents neuronal injury in kainate-induced seizure via disassembly of glur6-psd-95-mlk3 signaling module. Neural Regen Res. 2014;9:2059–2065.
  • Rangel A, Burgaya F, Gavin R, et al. Enhanced susceptibility of prnp-deficient mice to kainate-induced seizures, neuronal apoptosis, and death: role of AMPA/kainate receptors. J Neurosci Res. 2007;85:2741–2755.
  • Carulla P, Bribian A, Rangel A, et al. Neuroprotective role of prpc against kainate-induced epileptic seizures and cell death depends on the modulation of jnk3 activation by glur6/7-psd-95 binding. Mol Biol Cell. 2011;22:3041–3054.
  • Wang Z, Chen Y, Lu Y, et al. Effects of jip3 on epileptic seizures: evidence from temporal lobe epilepsy patients, kainic-induced acute seizures and pentylenetetrazole-induced kindled seizures. Neuroscience. 2015;300:314–324.
  • Whitmarsh AJ, Kuan CY, Kennedy NJ, et al. Requirement of the jip1 scaffold protein for stress-induced jnk activation. Genes Dev. 2001;15:2421–2432.
  • Magara F, Haefliger JA, Thompson N, et al. Increased vulnerability to kainic acid-induced epileptic seizures in mice underexpressing the scaffold protein islet-brain 1/jip-1. Eur J Neurosci. 2003;17:2602–2610.
  • Checker R, Gambhir L, Sharma D, et al. Plumbagin induces apoptosis in lymphoma cells via oxidative stress mediated glutathionylation and inhibition of mitogen-activated protein kinase phosphatases (mkp1/2). Cancer Lett. 2015;357:265–278.
  • Zdrojewska J, Coffey ET. The impact of jnk on neuronal migration. Adv Exp Med Biol. 2014;800:37–57.
  • Schauwecker PE. Seizure-induced neuronal death is associated with induction of c-jun n-terminal kinase and is dependent on genetic background. Brain Res. 2000;884:116–128.
  • Cole-Edwards KK, Musto AE, Bazan NG. C-jun n-terminal kinase activation responses induced by hippocampal kindling are mediated by reactive astrocytes. J Neurosci. 2006;26:8295–8304.
  • Zhao Y, Spigolon G, Bonny C, et al. The jnk inhibitor d-jnki-1 blocks apoptotic jnk signaling in brain mitochondria. Mol Cell Neurosci. 2012;49:300–310.
  • Yang DD, Kuan CY, Whitmarsh AJ, et al. Absence of excitotoxicity-induced apoptosis in the hippocampus of mice lacking the jnk3 gene. Nature. 1997;389:865–870.
  • Fan M, Chambers TC. Role of mitogen-activated protein kinases in the response of tumor cells to chemotherapy. Drug Resist Updat. 2001;4:253–267.
  • Han SR, Shin C, Park S, et al. Differential expression of activating transcription factor-2 and c-jun in the immature and adult rat hippocampus following lithium-pilocarpine induced status epilepticus. Yonsei Med J. 2009;50:200–205.
  • Murphy BM, Engel T, Paucard A, et al. Contrasting patterns of bim induction and neuroprotection in bim-deficient mice between hippocampus and neocortex after status epilepticus. Cell Death Differ. 2010;17:459–468.
  • Putcha GV, Le S, Frank S, et al. Jnk-mediated bim phosphorylation potentiates bax-dependent apoptosis. Neuron. 2003;38:899–914.
  • Li C, Xu B, Wang WW, et al. Coactivation of Gaba receptors inhibits the jnk3 apoptotic pathway via disassembly of glur6-psd-95-mlk3 signaling module in ka-induced seizure. Epilepsia. 2010;51:391–403.
  • de Lemos L, Junyent F, Verdaguer E, et al. Differences in activation of erk1/2 and p38 kinase in jnk3 null mice following ka treatment. J Neurochem. 2010;114:1315–1322.
  • Kim JY, Yu SJ, Oh HJ, et al. Panaxydol induces apoptosis through an increased intracellular calcium level, activation of jnk and p38 mapk and NADPH oxidase-dependent generation of reactive oxygen species. Apoptosis. 2011;16:347–358.
  • Walker MC. Pathophysiology of status epilepticus. Neurosci Lett. 2018;667:84–91.
  • Bernard A, Klionsky DJ. Defining the membrane precursor supporting the nucleation of the phagophore. Autophagy. 2014;10:1–2.
  • Dong Y, Wang S, Zhang T, et al. Ascorbic acid ameliorates seizures and brain damage in rats through inhibiting autophagy. Brain Res. 2013;1535:115–123.
  • Hussein AM, Adel M, El-Mesery M, et al. L-carnitine modulates epileptic seizures in pentylenetetrazole-kindled rats via suppression of apoptosis and autophagy and upregulation of hsp70. Brain Sci. 2018;8:45.
  • Wu Q, Yi X. Down-regulation of long noncoding RNA malat1 protects hippocampal neurons against excessive autophagy and apoptosis via the pi3k/Akt signaling pathway in rats with epilepsy. J Mol Neurosci. 2018;65:234–245.
  • Wang L, Song LF, Chen XY, et al. Mir-181b inhibits p38/jnk signaling pathway to attenuate autophagy and apoptosis in juvenile rats with kainic acid-induced epilepsy via targeting tlr4. CNS Neurosci Ther. 2018;25:112–122.
  • van der Vos KE, Gomez-Puerto C, Coffer PJ. Regulation of autophagy by forkhead box (fox) o transcription factors. Adv Biol Regul. 2012;52:122–136.
  • Luo S, Garcia-Arencibia M, Zhao R, et al. Bim inhibits autophagy by recruiting beclin 1 to microtubules. Mol Cell. 2012;47:359–370.
  • Binder DK. Astrocytes: stars of the sacred disease. Epilepsy Curr. 2018;18:172–179.
  • Heuser K, Szokol K, Tauboll E. The role of glial cells in epilepsy. Tidsskr Nor Laegeforen. 2014;134:37–41.
  • Eid T, Lee TS, Thomas MJ, et al. Loss of perivascular aquaporin 4 may underlie deficient water and k + homeostasis in the human epileptogenic hippocampus. Proc Natl Acad Sci USA. 2005;102:1193–1198.
  • Alvestad S, Hammer J, Hoddevik EH, et al. Mislocalization of aqp4 precedes chronic seizures in the kainate model of temporal lobe epilepsy. Epilepsy Res. 2013;105:30–41.
  • Salman MM, Sheilabi MA, Bhattacharyya D, et al. Transcriptome analysis suggests a role for the differential expression of cerebral aquaporins and the mapk signalling pathway in human temporal lobe epilepsy. Eur J Neurosci. 2017;46:2121–2132.
  • Tang L, Lu Y, Zheng W, et al. Overexpression of map-2 via formation of microtubules plays an important role in the sprouting of mossy fibers in epileptic rats. J Mol Neurosci. 2014;53:103–108.
  • Sanchez C, Diaz-Nido J, Avila J. Phosphorylation of microtubule-associated protein 2 (map2) and its relevance for the regulation of the neuronal cytoskeleton function. Prog Neurobiol. 2000;61:133–168.
  • Chang L, Jones Y, Ellisman MH, et al. Jnk1 is required for maintenance of neuronal microtubules and controls phosphorylation of microtubule-associated proteins. Dev Cell. 2003;4:521–533.
  • Won KJ, Park SH, Park T, et al. Cofilin phosphorylation mediates proliferation in response to platelet-derived growth factor-bb in rat aortic smooth muscle cells. J Pharmacol Sci. 2008;108:372–379.
  • Sun T, Yu N, Zhai LK, et al. C-jun nh2-terminal kinase (jnk)-interacting protein-3 (jip3) regulates neuronal axon elongation in a kinesin- and jnk-dependent manner. J Biol Chem. 2013;288:14531–14543.
  • Yang H, Courtney MJ, Martinsson P, et al. Hippocampal long-term depression is enhanced, depotentiation is inhibited and long-term potentiation is unaffected by the application of a selective c-jun n-terminal kinase inhibitor to freely behaving rats. Eur J Neurosci. 2011;33:1647–1655.
  • Curran BP, Murray HJ, O’Connor JJ. A role for c-jun n-terminal kinase in the inhibition of long-term potentiation by interleukin-1beta and long-term depression in the rat dentate gyrus in vitro. Neuroscience. 2003;118:347–357.
  • Wiltshire C, Matsushita M, Tsukada S, et al. A new c-jun n-terminal kinase (jnk)-interacting protein, sab (sh3bp5), associates with mitochondria. Biochem J. 2002;367:577–585.
  • Sodero AO, Rodriguez-Silva M, Salio C, et al. Sab is differentially expressed in the brain and affects neuronal activity. Brain Res. 2017;1670:76–85.
  • Noh HS, Kim DW, Kang SS, et al. Ketogenic diet decreases the level of proenkephalin mRNA induced by kainic acid in the mouse hippocampus. Neurosci Lett. 2006;395:87–92.
  • Douglass J, Grimes L, Shook J, et al. Systemic administration of kainic acid differentially regulates the levels of prodynorphin and proenkephalin mRNA and peptides in the rat hippocampus. Brain Res Mol Brain Res. 1991;9:79–86.
  • Hsieh CL, Lin JJ, Chiang SY, et al. Gastrodia elata modulated activator protein 1 via c-jun n-terminal kinase signaling pathway in kainic acid-induced epilepsy in rats. J Ethnopharmacol. 2007;109:241–247.
  • Hsieh CL, Ho TY, Su SY, et al. Uncaria rhynchophylla and rhynchophylline inhibit c-jun n-terminal kinase phosphorylation and nuclear factor-kappa B activity in kainic acid-treated rats. Am J Chin Med. 2009;37:351–360.
  • Zhang R, Yang G, Wang Q, et al. Acylated ghrelin protects hippocampal neurons in pilocarpine-induced seizures of immature rats by inhibiting cell apoptosis. Mol Biol Rep. 2013;40:51–58.
  • Busquets O, Ettcheto M, Verdaguer E, et al. Jnk1 inhibition by licochalcone a leads to neuronal protection against excitotoxic insults derived of kainic acid. Neuropharmacology. 2018;131:440–452.
  • Xu X, Hu Y, Xiong Y, et al. Association of microtubule dynamics with chronic epilepsy. Mol Neurobiol. 2016;53:5013–5024.
  • Semaan S, Wu J, Gan Y, et al. Hyperactivation of bdnf-trkb signaling cascades in human hypothalamic hamartoma (hh): a potential mechanism contributing to epileptogenesis. CNS Neurosci Ther. 2015;21:164–172.

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