Skip to content
2000
Cover image Placeholder

Abstract

Epilepsy is a common neurological condition marked by frequent seizures, which often accompanies cognitive and psychological difficulties. With an estimated 65 million sufferers worldwide, epilepsy imposes an enormous burden on individuals, families, and healthcare systems. Seizures are categorized into focal, generalized, and seizures with unknown onset. Of all the focal seizures, temporal lobe epilepsy (TLE) is distinctive as it develops in the temporal lobes and causes altered consciousness as well as emotional difficulties. About 30% of people with TLE continue to have symptoms that do not improve with antiepileptic medications, resulting in further physical and psychological issues. Oxidative stress (OS) plays a pivotal role in the pathophysiology of epilepsy, driven by an overproduction of reactive oxygen species (ROS). Mitochondrial dysfunction and the accumulation of ROS disrupt neuronal calcium homeostasis, increase synaptic excitability, and contribute to neuronal injury and death. Antioxidant enzymes like catalase and superoxide dismutase help to reduce damage caused by ROS; yet, prolonged OS promotes the development of epileptogenesis. Additionally, recent research highlights the transcription factor nuclear factor erythroid 2–related factor 2 (Nrf2), a key regulator of cellular defense against OS. Activation of the Nrf2-antioxidant response elements (ARE) signaling pathway enhances antioxidant enzyme expression and protects neurons from ROS damage. Studies suggest that targeting Nrf2 could offer novel therapeutic strategies for epilepsy by reducing OS and improving neuronal survival. Exploring Nrf2-activating compounds holds promise for developing more effective antiepileptic therapies, addressing the unmet need for treatments that can modulate the oxidative environment within the brain.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/cmccnsa/10.2174/0118715249377844250806052840
2025-09-16
2025-09-27

  • From This Site

    /content/journals/cmccnsa/10.2174/0118715249377844250806052840
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. Fisher R.S. Acevedo C. Arzimanoglou A. Bogacz A. Cross J.H. Elger C.E. Engel J. Jr Forsgren L. French J.A. Glynn M. Hesdorffer D.C. Lee B.I. Mathern G.W. Moshé S.L. Perucca E. Scheffer I.E. Tomson T. Watanabe M. Wiebe S. ILAE Official Report: A practical clinical definition of epilepsy. Epilepsia 2014 55 4 475 482 10.1111/epi.12550 24730690
    [Google Scholar]
  2. Sarmast S.T. Abdullahi A.M. Jahan N. Current classification of seizures and epilepsies: Scope, limitations and recommendations for future action. Cureus 2020 12 9 10549 10.7759/cureus.10549 33101797
    [Google Scholar]
  3. Mesraoua B. Deleu D. Hassan A.H. Gayane M. Lubna A. Ali M.A. Tomson T. Khalil B.A. Cross J.H. Asadi-Pooya A.A. Dramatic outcomes in epilepsy: Depression, suicide, injuries, and mortality. Curr. Med. Res. Opin. 2020 36 9 1473 1480 10.1080/03007995.2020.1776234 32476500
    [Google Scholar]
  4. Qaiser F. Yuen R.K.C. Andrade D.M. Genetics of epileptic networks: From focal to generalized genetic epilepsies. Curr. Neurol. Neurosci. Rep. 2020 20 10 46 10.1007/s11910‑020‑01059‑x 32789700
    [Google Scholar]
  5. Périn B. Szurhaj W. New onset refractory status epilepticus: State of the art. Rev. Neurol. 2022 178 1-2 74 83 10.1016/j.neurol.2021.12.005 35031143
    [Google Scholar]
  6. Wirrell E.C. Classification of Seizures and the Epilepsies. John Wiley & Sons 2021 11 22 10.1002/9781119431893.ch2
    [Google Scholar]
  7. Kayabas M.A. Köksal Ersöz E. Yochum M. Bartolomei F. Benquet P. Wendling F. Transition to seizure in focal epilepsy: From SEEG phenomenology to underlying mechanisms. Epilepsia 2024 65 12 3619 3630 10.1111/epi.18173 39474858
    [Google Scholar]
  8. Ballerini A. Tondelli M. Talami F. Molinari M.A. Micalizzi E. Giovannini G. Turchi G. Malagoli M. Genovese M. Meletti S. Vaudano A.E. Amygdala subnuclear volumes in temporal lobe epilepsy with hippocampal sclerosis and in non-lesional patients. Brain Commun. 2022 4 5 fcac225 10.1093/braincomms/fcac225 36213310
    [Google Scholar]
  9. Katyal R. Classification and diagnosis of epilepsy. Continuum 2025 31 1 14 37 10.1212/CON.0000000000001519 39899094
    [Google Scholar]
  10. Fisher R.S. The new classification of seizures by the international league against epilepsy 2017. Curr. Neurol. Neurosci. Rep. 2017 17 6 48 10.1007/s11910‑017‑0758‑6 28425015
    [Google Scholar]
  11. Zhou Z. Gong P. Jiao X. Niu Y. Xu Z. Qin J. Yang Z. A generalized seizure type: Myoclonic-to-tonic seizure. Clin. Neurophysiol. 2024 164 24 29 10.1016/j.clinph.2024.04.011 38823261
    [Google Scholar]
  12. Riva A. D’Onofrio G. Ferlazzo E. Pascarella A. Pasini E. Franceschetti S. Panzica F. Canafoglia L. Vignoli A. Coppola A. Badioni V. Beccaria F. Labate A. Gambardella A. Romeo A. Capovilla G. Michelucci R. Striano P. Belcastro V. Myoclonus: Differential diagnosis and current management. Epilepsia Open 2024 9 2 486 500 10.1002/epi4.12917 38334331
    [Google Scholar]
  13. Chandarana M. Saraf U. Divya K.P. Krishnan S. Kishore A. Myoclonus-A review. Ann. Indian Acad. Neurol. 2021 24 3 327 338 10.4103/aian.AIAN_1180_20 34446993
    [Google Scholar]
  14. Saxena S. Singh S.P. Makhija K. Seizure Disorders 66. Fam. Med. 2017 823
    [Google Scholar]
  15. Patel P. Moshé S.L. The evolution of the concepts of seizures and epilepsy: What’s in a name? Epilepsia Open 2020 5 1 22 35 10.1002/epi4.12375 32140641
    [Google Scholar]
  16. Milligan T.A. Epilepsy: A clinical overview. Am. J. Med. 2021 134 7 840 847 10.1016/j.amjmed.2021.01.038 33775643
    [Google Scholar]
  17. Henning O. Heuser K. Larsen V.S. Kyte E.B. Kostov H. Marthinsen P.B. Egge A. Alfstad K.Å. Nakken K.O. Temporal lobe epilepsy. Tidsskr. Nor. Laegeforen. 2023 143 2 10.4045/tidsskr.22.0369 36718887
    [Google Scholar]
  18. Carmona-Aparicio L. Pérez-Cruz C. Zavala-Tecuapetla C. Granados-Rojas L. Rivera-Espinosa L. Montesinos-Correa H. Hernández-Damián J. Pedraza-Chaverri J. Sampieri A. III Coballase-Urrutia E. Cárdenas-Rodríguez N. Overview of Nrf2 as therapeutic target in epilepsy. Int. J. Mol. Sci. 2015 16 8 18348 18367 10.3390/ijms160818348 26262608
    [Google Scholar]
  19. Stanley M. Chippa V. Aeddula N.R. Quintanilla Rodriguez B.S. Adigun R. Rhabdomyolysis. 2022. StatPearls. StatPearls Publishing Treasure Island, FL 2022
    [Google Scholar]
  20. Yadav J. Singh P. Dabla S. Gupta R. Psychiatric comorbidity and quality of life in patients with epilepsy on anti-epileptic monotherapy and polytherapy. Tzu-Chi Med. J. 2022 34 2 226 231 10.4103/tcmj.tcmj_34_21 35465291
    [Google Scholar]
  21. Smith E.H. Merricks E.M. Liou J.Y. Casadei C. Melloni L. Thesen T. Friedman D.J. Doyle W.K. Emerson R.G. Goodman R.R. McKhann G.M. II Sheth S.A. Rolston J.D. Schevon C.A. Dual mechanisms of ictal high frequency oscillations in human rhythmic onset seizures. Sci. Rep. 2020 10 1 19166 10.1038/s41598‑020‑76138‑7 33154490
    [Google Scholar]
  22. van Lanen R.H.G.J. Melchers S. Hoogland G. Schijns O.E.M.G. Zandvoort M.A.M.J. Haeren R.H.L. Rijkers K. Microvascular changes associated with epilepsy: A narrative review. J. Cereb. Blood Flow Metab. 2021 41 10 2492 2509 10.1177/0271678X211010388 33866850
    [Google Scholar]
  23. Matovu D. Cavalheiro E.A. Differences in evolution of epileptic seizures and topographical distribution of tissue damage in selected limbic structures between male and female rats submitted to the pilocarpine model. Front. Neurol. 2022 13 802587 10.3389/fneur.2022.802587 35449517
    [Google Scholar]
  24. Kharibegashvili A. Neurochemical theory of epilepsy pathogenesis in it’s neurological and mental manifestations. Am J Psychiatry Neurosci 2020 8 2 37 43 10.11648/j.ajpn.20200802.13
    [Google Scholar]
  25. Mastrangelo M. Epilepsy in inherited neurotransmitter disorders: Spotlights on pathophysiology and clinical management. Metab. Brain Dis. 2021 36 1 29 43 10.1007/s11011‑020‑00635‑x 33095372
    [Google Scholar]
  26. Zhang J. Huang J.H. Wang F. Qi X. Astrocytic modulation of potassium under seizures. Neural Regen. Res. 2020 15 6 980 987 10.4103/1673‑5374.270295 31823867
    [Google Scholar]
  27. Gędek A. Materna M. Majewski P. Antosik A.Z. Dominiak M. Electrolyte disturbances related to sodium and potassium and electroconvulsive therapy: A systematic review. J. Clin. Med. 2023 12 20 6677 10.3390/jcm12206677 37892815
    [Google Scholar]
  28. Kundap U.P. Paudel Y.N. Shaikh M.F. Animal models of metabolic epilepsy and epilepsy associated metabolic dysfunction: A systematic review. Pharmaceuticals 2020 13 6 106 10.3390/ph13060106 32466498
    [Google Scholar]
  29. Sun H. Li X. Guo Q. Liu S. Research progress on oxidative stress regulating different types of neuronal death caused by epileptic seizures. Neurol. Sci. 2022 43 11 6279 6298 10.1007/s10072‑022‑06302‑6 35927358
    [Google Scholar]
  30. Zhang Y. Zhang M. Zhu W. Yu J. Wang Q. Zhang J. Cui Y. Pan X. Gao X. Sun H. Succinate accumulation induces mitochondrial reactive oxygen species generation and promotes status epilepticus in the kainic acid rat model. Redox Biol. 2020 28 101365 10.1016/j.redox.2019.101365 31707354
    [Google Scholar]
  31. Medina-Ceja L. Pardo-Peña K. Morales-Villagrán A. Oxidative stress markers in seizures and epilepsy: Methods and applications to models. Oxidative Stress and Dietary Antioxidants in Neurological Diseases. Academic Press Cambridge, Massachusetts 2020 109 122 10.1016/B978‑0‑12‑817780‑8.00008‑6
    [Google Scholar]
  32. Mayorga-Weber G. Rivera F.J. Castro M.A. Neuron‐glia (mis)interactions in brain energy metabolism during aging. J. Neurosci. Res. 2022 100 3 835 854 10.1002/jnr.25015 35085408
    [Google Scholar]
  33. Chaudhary M.R. Chaudhary S. Sharma Y. Singh T.A. Mishra A.K. Sharma S. Mehdi M.M. Aging, oxidative stress and degenerative diseases: Mechanisms, complications and emerging therapeutic strategies. Biogerontology 2023 24 5 609 662 10.1007/s10522‑023‑10050‑1 37516673
    [Google Scholar]
  34. Lee K.H. Cha M. Lee B.H. Crosstalk between neuron and glial cells in oxidative injury and neuroprotection. Int. J. Mol. Sci. 2021 22 24 13315 10.3390/ijms222413315 34948108
    [Google Scholar]
  35. Rosa A.C. Corsi D. Cavi N. Bruni N. Dosio F. Superoxide dismutase administration: A review of proposed human uses. Molecules 2021 26 7 1844 10.3390/molecules26071844 33805942
    [Google Scholar]
  36. Saxena P. Selvaraj K. Khare S.K. Chaudhary N. Superoxide dismutase as multipotent therapeutic antioxidant enzyme: Role in human diseases. Biotechnol. Lett. 2022 44 1 1 22 10.1007/s10529‑021‑03200‑3 34734354
    [Google Scholar]
  37. Andrés C.M.C. Pérez de la Lastra J.M. Juan C.A. Plou F.J. Pérez-Lebeña E. Chemistry of hydrogen peroxide formation and elimination in mammalian cells, and its role in various pathologies. Stresses 2022 2 3 256 274 10.3390/stresses2030019
    [Google Scholar]
  38. Pei J. Pan X. Wei G. Hua Y. Research progress of glutathione peroxidase family (GPX) in redoxidation. Front. Pharmacol. 2023 14 1147414 10.3389/fphar.2023.1147414 36937839
    [Google Scholar]
  39. Manco G. Porzio E. Carusone T.M. Human paraoxonase-2 (PON2): Protein functions and modulation. Antioxidants 2021 10 2 256 10.3390/antiox10020256 33562328
    [Google Scholar]
  40. Abdulmalek D.S. Paraoxonase 2 (PON2) in Cardiovascular Disease (CVD): The Role of PON2 in Acute Myocardial Ischemia-Reperfusion Injury and Diet-Induced Obesity. University of California Los Angeles 2020
    [Google Scholar]
  41. Fumarola S. Cecati M. Sartini D. Ferretti G. Milanese G. Galosi A.B. Pozzi V. Campagna R. Morresi C. Emanuelli M. Bacchetti T. Bladder cancer chemosensitivity is affected by paraoxonase-2 expression. Antioxidants 2020 9 2 175 10.3390/antiox9020175 32093309
    [Google Scholar]
  42. Armeni T. Principato G. Glutathione, an over one billion years ancient molecule, is still actively involved in cell regulatory pathways. The First Outstanding 50 Years of “Università Politecnica delle Marche. Springer Cham 2020 10.1007/978‑3‑030‑33832‑9_28
    [Google Scholar]
  43. Dwivedi D. Megha K. Mishra R. Mandal P.K. Glutathione in brain: Overview of its conformations, functions, biochemical characteristics, quantitation and potential therapeutic role in brain disorders. Neurochem. Res. 2020 45 7 1461 1480 10.1007/s11064‑020‑03030‑1 32297027
    [Google Scholar]
  44. Pinchuk I. Kohen R. Stuetz W. Weber D. Franceschi C. Capri M. Hurme M. Grubeck-Loebenstein B. Schön C. Bernhardt J. Debacq-Chainiaux F. Dollé M.E.T. Jansen E.H.J.M. Gonos E.S. Sikora E. Breusing N. Gradinaru D. Moreno-Villanueva M. Bürkle A. Grune T. Lichtenberg D. Do low molecular weight antioxidants contribute to the Protection against oxidative damage? The interrelation between oxidative stress and low molecular weight antioxidants based on data from the MARK-AGE study. Arch. Biochem. Biophys. 2021 713 109061 10.1016/j.abb.2021.109061 34662556
    [Google Scholar]
  45. Goncalves R.L.S. Watson M.A. Wong H.S. Orr A.L. Brand M.D. The use of site-specific suppressors to measure the relative contributions of different mitochondrial sites to skeletal muscle superoxide and hydrogen peroxide production. Redox Biol. 2020 28 101341 10.1016/j.redox.2019.101341 31627168
    [Google Scholar]
  46. Vilchis-Landeros M.M. Matuz-Mares D. Vázquez-Meza H. Regulation of metabolic processes by hydrogen peroxide generated by NADPH oxidases. Processes 2020 8 11 1424 10.3390/pr8111424
    [Google Scholar]
  47. Bedard K. Krause K.H. The NOX family of ROS-generating NADPH oxidases: Physiology and pathophysiology. Physiol. Rev. 2007 87 1 245 313 10.1152/physrev.00044.2005 17237347
    [Google Scholar]
  48. Hou L. Zhang L. Hong J.S. Zhang D. Zhao J. Wang Q. Nicotinamide adenine dinucleotide phosphate oxidase and neurodegenerative diseases: Mechanisms and therapy. Antioxid. Redox Signal. 2020 33 5 374 393 10.1089/ars.2019.8014 31968994
    [Google Scholar]
  49. Tu D. Velagapudi R. Gao Y. Hong J.S. Zhou H. Gao H.M. Activation of neuronal NADPH oxidase NOX2 promotes inflammatory neurodegeneration. Free Radic. Biol. Med. 2023 200 47 58 10.1016/j.freeradbiomed.2023.03.001 36870375
    [Google Scholar]
  50. Malkov A. Ivanov A.I. Latyshkova A. Bregestovski P. Zilberter M. Zilberter Y. Activation of nicotinamide adenine dinucleotide phosphate oxidase is the primary trigger of epileptic seizures in rodent models. Ann. Neurol. 2019 85 6 907 920 10.1002/ana.25474 30937971
    [Google Scholar]
  51. Puttachary S. Sharma S. Stark S. Thippeswamy T. Seizure-induced oxidative stress in temporal lobe epilepsy. BioMed Res. Int. 2015 2015 1 1 20 10.1155/2015/745613 25650148
    [Google Scholar]
  52. Geronzi U. Lotti F. Grosso S. Oxidative stress in epilepsy. Expert Rev. Neurother. 2018 18 5 427 434 10.1080/14737175.2018.1465410 29651881
    [Google Scholar]
  53. Patel M. Mitochondrial dysfunction and oxidative stress: Cause and consequence of epileptic seizures. Free Radic. Biol. Med. 2004 37 12 1951 1962 10.1016/j.freeradbiomed.2004.08.021 15544915
    [Google Scholar]
  54. Jarrett S.G. Liang L.P. Hellier J.L. Staley K.J. Patel M. Mitochondrial DNA damage and impaired base excision repair during epileptogenesis. Neurobiol. Dis. 2008 30 1 130 138 10.1016/j.nbd.2007.12.009 18295498
    [Google Scholar]
  55. Pauletti A Terrone G Shekh-Ahmad T Salamone A Ravizza T Rizzi M Pastore A Pascente R Liang LP Villa BR Balosso S Targeting oxidative stress improves disease outcomes in a rat model of acquired epilepsy. Brain 2019 142 7 e39 10.1093/brain/awz130 31145451
    [Google Scholar]
  56. Liang L.P. Patel M. Mitochondrial oxidative stress and increased seizure susceptibility in Sod2−/+ mice. Free Radic. Biol. Med. 2004 36 5 542 554 10.1016/j.freeradbiomed.2003.11.029 14980699
    [Google Scholar]
  57. Xie W. Koppula S. Kale M.B. Ali L.S. Wankhede N.L. Umare M.D. Upaganlawar A.B. Abdeen A. Ebrahim E.E. El-Sherbiny M. Behl T. Shen B. Singla R.K. Unraveling the nexus of age, epilepsy, and mitochondria: exploring the dynamics of cellular energy and excitability. Front. Pharmacol. 2024 15 1469053 10.3389/fphar.2024.1469053 39309002
    [Google Scholar]
  58. Kang H.C. Lee Y.M. Kim H.D. Mitochondrial disease and epilepsy. Brain Dev. 2013 35 8 757 761 10.1016/j.braindev.2013.01.006 23414619
    [Google Scholar]
  59. Kunz W.S. Kudin A.P. Vielhaber S. Blümcke I. Zuschratter W. Schramm J. Beck H. Elger C.E. Mitochondrial complex I deficiency in the epileptic focus of patients with temporal lobe epilepsy. Ann. Neurol. 2000 48 5 766 773 10.1002/1531‑8249(200011)48:5<766::AID‑ANA10>3.0.CO;2‑M 11079540
    [Google Scholar]
  60. Zsurka G. Kunz W.S. Mitochondrial dysfunction and seizures: The neuronal energy crisis. Lancet Neurol. 2015 14 9 956 966 10.1016/S1474‑4422(15)00148‑9 26293567
    [Google Scholar]
  61. Sandouka S. Shekh-Ahmad T. Induction of the Nrf2 pathway by sulforaphane is neuroprotective in a rat temporal lobe epilepsy model. Antioxidants 2021 10 11 1702 10.3390/antiox10111702 34829573
    [Google Scholar]
  62. He F. Ru X. Wen T. NRF2, a transcription factor for stress response and beyond. Int. J. Mol. Sci. 2020 21 13 4777 10.3390/ijms21134777 32640524
    [Google Scholar]
  63. Ngo V.Y. Nrf2 regulation by Hsp90, oxidation, and in breast cancer. Electronic thesis and dissertation repository 2021
    [Google Scholar]
  64. Ngo V. Duennwald M.L. Nrf2 and oxidative stress: A general overview of mechanisms and implications in human disease. Antioxidants 2022 11 12 2345 10.3390/antiox11122345 36552553
    [Google Scholar]
  65. Lu Y. An L. Taylor M.R.G. Chen Q.M. Nrf2 signaling in heart failure: Expression of Nrf2, Keap1, antioxidant, and detoxification genes in dilated or ischemic cardiomyopathy. Physiol. Genomics 2022 54 3 115 127 10.1152/physiolgenomics.00079.2021 35073209
    [Google Scholar]
  66. Ibrahim L. Mesgarzadeh J. Xu I. Powers E.T. Wiseman R.L. Bollong M.J. Defining the functional targets of Cap ‘n’collar transcription factors NRF1, NRF2, and NRF3. Antioxidants 2020 9 10 1025 10.3390/antiox9101025 33096892
    [Google Scholar]
  67. Zhang Y. Shi Z. Zhou Y. Xiao Q. Wang H. Peng Y. Emerging substrate proteins of kelch-like ECH associated protein 1 (Keap1) and potential challenges for the development of small-molecule inhibitors of the Keap1-nuclear factor erythroid 2-related factor 2 (Nrf2) protein–protein interaction. J. Med. Chem. 2020 63 15 7986 8002 10.1021/acs.jmedchem.9b01865 32233486
    [Google Scholar]
  68. Shilovsky G.A. Dibrova D.V. Regulation of cell proliferation and Nrf2-mediated antioxidant defense: Conservation of Keap1 cysteines and Nrf2 binding site in the context of the evolution of KLHL family. Life 2023 13 4 1045 10.3390/life13041045 37109574
    [Google Scholar]
  69. Dayalan Naidu S. Dinkova-Kostova A.T. KEAP1, a cysteine-based sensor and a drug target for the prevention and treatment of chronic disease. Open Biol. 2020 10 6 200105 10.1098/rsob.200105 32574549
    [Google Scholar]
  70. Unoki T. Akiyama M. Kumagai Y. Nrf2 activation and its coordination with the protective defense systems in response to electrophilic stress. Int. J. Mol. Sci. 2020 21 2 545 10.3390/ijms21020545 31952233
    [Google Scholar]
  71. Meng X. Waddington J.C. Tailor A. Lister A. Hamlett J. Berry N. Park B.K. Sporn M.B. CDDO-imidazolide targets multiple amino acid residues on the Nrf2 adaptor, Keap1. J. Med. Chem. 2020 63 17 9965 9976 10.1021/acs.jmedchem.0c01088 32787104
    [Google Scholar]
  72. Kopacz A. Kloska D. Forman H.J. Jozkowicz A. Grochot-Przeczek A. Beyond repression of Nrf2: An update on Keap1. Free Radic. Biol. Med. 2020 157 63 74 10.1016/j.freeradbiomed.2020.03.023 32234331
    [Google Scholar]
  73. Crisman E. Duarte P. Dauden E. Cuadrado A. Rodríguez-Franco M.I. López M.G. León R. KEAP1‐NRF2 protein–protein interaction inhibitors: Design, pharmacological properties and therapeutic potential. Med. Res. Rev. 2023 43 1 237 287 10.1002/med.21925 36086898
    [Google Scholar]
  74. Bityutsky V.S. Tsekhmistrenko S.I. Tsekhmistrenko О.S. Tymoshok N.O. Spivak M.Y. Regulation of redox processes in biological systems with the participation of the Keap1/Nrf2/ARE signaling pathway, biogenic selenium nanoparticles as Nrf2 activators. Regul. Mech. Biosyst. 2020 11 4 483 493 10.15421/022074
    [Google Scholar]
  75. Suzuki T. Takahashi J. Yamamoto M. Molecular basis of the KEAP1-NRF2 signaling pathway. Mol. Cells 2023 46 3 133 141 10.14348/molcells.2023.0028 36994473
    [Google Scholar]
  76. Song M.Y. Lee D.Y. Chun K.S. Kim E.H. The role of NRF2/KEAP1 signaling pathway in cancer metabolism. Int. J. Mol. Sci. 2021 22 9 4376 10.3390/ijms22094376 33922165
    [Google Scholar]
  77. Kishore M. Pradeep M. Narne P. Jayalakshmi S. Panigrahi M. Patil A. Babu P.P. Regulation of Keap1-Nrf2 axis in temporal lobe epilepsy—hippocampal sclerosis patients may limit the seizure outcomes. Neurol. Sci. 2023 44 12 4441 4450 10.1007/s10072‑023‑06936‑0 37432566
    [Google Scholar]
  78. Otsuki A. Yamamoto M. Cis-element architecture of Nrf2–sMaf heterodimer binding sites and its relation to diseases. Arch. Pharm. Res. 2020 43 3 275 285 10.1007/s12272‑019‑01193‑2 31792803
    [Google Scholar]
  79. Wang N. Wang W. Sadiq F.A. Wang S. Caiqin L. Jianchang J. Involvement of Nrf2 and Keap1 in the activation of antioxidant responsive element (ARE) by chemopreventive agent peptides from soft-shelled turtle. Process Biochem. 2020 92 174 181 10.1016/j.procbio.2019.12.022
    [Google Scholar]
  80. Priestley J.R.C. Kautenburg K.E. Casati M.C. Endres B.T. Geurts A.M. Lombard J.H. The NRF2 knockout rat: A new animal model to study endothelial dysfunction, oxidant stress, and microvascular rarefaction. Am. J. Physiol. Heart Circ. Physiol. 2016 310 4 H478 H487 10.1152/ajpheart.00586.2015 26637559
    [Google Scholar]
  81. Hannan M.A. Dash R. Sohag A.A.M. Haque M.N. Moon I.S. Neuroprotection against oxidative stress: Phytochemicals targeting TrkB signaling and the Nrf2-ARE antioxidant system. Front. Mol. Neurosci. 2020 13 116 10.3389/fnmol.2020.00116 32714148
    [Google Scholar]
  82. Yang N. Guan Q.W. Chen F.H. Xia Q.X. Yin X.X. Zhou H.H. Mao X.Y. Antioxidants targeting mitochondrial oxidative stress: Promising neuroprotectants for epilepsy. Oxid. Med. Cell. Longev. 2020 2020 1 1 14 10.1155/2020/6687185 33299529
    [Google Scholar]
  83. Manavi M.A. Mohammad Jafari R. Shafaroodi H. Dehpour A.R. The Keap1/Nrf2/ARE/HO-1 axis in epilepsy: Crosstalk between oxidative stress and neuroinflammation. Int. Immunopharmacol. 2025 153 114304 10.1016/j.intimp.2025.114304 40117806
    [Google Scholar]
  84. Takata F. Nakagawa S. Matsumoto J. Dohgu S. Blood-brain barrier dysfunction amplifies the development of neuroinflammation: understanding of cellular events in brain microvascular endothelial cells for prevention and treatment of BBB dysfunction. Front. Cell. Neurosci. 2021 15 661838 10.3389/fncel.2021.661838 34588955
    [Google Scholar]
  85. Zgorzynska E. Dziedzic B. Walczewska A. An overview of the Nrf2/ARE pathway and its role in neurodegenerative diseases. Int. J. Mol. Sci. 2021 22 17 9592 10.3390/ijms22179592 34502501
    [Google Scholar]
  86. Zhang M. An C. Gao Y. Leak R.K. Chen J. Zhang F. Emerging roles of Nrf2 and phase II antioxidant enzymes in neuroprotection. Prog. Neurobiol. 2013 100 30 47 10.1016/j.pneurobio.2012.09.003 23025925
    [Google Scholar]
  87. Milder J.B. Liang L.P. Patel M. Acute oxidative stress and systemic Nrf2 activation by the ketogenic diet. Neurobiol. Dis. 2010 40 1 238 244 10.1016/j.nbd.2010.05.030 20594978
    [Google Scholar]
  88. Wang W. Wu Y. Zhang G. Fang H. Wang H. Zang H. Xie T. Wang W. Activation of Nrf2-ARE signal pathway protects the brain from damage induced by epileptic seizure. Brain Res. 2014 1544 54 61 10.1016/j.brainres.2013.12.004 24333359
    [Google Scholar]
  89. Mazzuferi M. Kumar G. van Eyll J. Danis B. Foerch P. Kaminski R.M. Nrf2 defense pathway: Experimental evidence for its protective role in epilepsy. Ann. Neurol. 2013 74 4 560 568 10.1002/ana.23940 23686862
    [Google Scholar]
  90. Wang W. Wang W. Zhang G. Wu Y. Xie T. Kan M. Fang H. Wang H. Activation of Nrf2-ARE signal pathway in hippocampus of amygdala kindling rats. Neurosci. Lett. 2013 543 58 63 10.1016/j.neulet.2013.03.038 23570726
    [Google Scholar]
  91. Xu P. Wang K. Lu C. Dong L. Gao L. Yan M. Aibai S. Yang Y. Liu X. The protective effect of lavender essential oil and its main component linalool against the cognitive deficits induced by D‐Galactose and aluminum trichloride in mice. Evid. Based Complement. Alternat. Med. 2017 2017 1 7426538 10.1155/2017/7426538 28529531
    [Google Scholar]
  92. Abou El-ezz D. Maher A. Sallam N. El-brairy A. Kenawy S. Trans-cinnamaldehyde modulates hippocampal Nrf2 factor and inhibits amyloid beta aggregation in LPS-induced neuroinflammation mouse model. Neurochem. Res. 2018 43 12 2333 2342 10.1007/s11064‑018‑2656‑y 30302613
    [Google Scholar]
  93. Jeong W.S. Kim I.W. Hu R. Kong A.N.T. Modulatory properties of various natural chemopreventive agents on the activation of NF-kappaB signaling pathway. Pharm. Res. 2004 21 4 661 670 10.1023/B:PHAM.0000022413.43212.cf 15139523
    [Google Scholar]
  94. Mascuch S.J. Boudreau P.D. Carland T.M. Pierce N.T. Olson J. Hensler M.E. Choi H. Campanale J. Hamdoun A. Nizet V. Gerwick W.H. Gaasterland T. Gerwick L. Marine natural product Honaucin A attenuates inflammation by activating the Nrf2-ARE pathway. J. Nat. Prod. 2018 81 3 506 514 10.1021/acs.jnatprod.7b00734 29215273
    [Google Scholar]
  95. Yang X. Yang R. Zhang F. Role of Nrf2 in Parkinson’s disease: Toward new perspectives. Front. Pharmacol. 2022 13 919233 10.3389/fphar.2022.919233 35814229
    [Google Scholar]
  96. Moreira S. Fonseca I. Nunes M.J. Rosa A. Lemos L. Rodrigues E. Carvalho A.N. Outeiro T.F. Rodrigues C.M.P. Gama M.J. Castro-Caldas M. Nrf2 activation by tauroursodeoxycholic acid in experimental models of Parkinson’s disease. Exp. Neurol. 2017 295 77 87 10.1016/j.expneurol.2017.05.009 28552716
    [Google Scholar]
  97. Ibrahim W.W. Abdel Rasheed N.O. Diapocynin neuroprotective effects in 3-nitropropionic acid Huntington’s disease model in rats: Emphasis on Sirt1/Nrf2 signaling pathway. Inflammopharmacology 2022 30 5 1745 1758 10.1007/s10787‑022‑01004‑z 35639233
    [Google Scholar]
  98. Rabelo A.C.S. de Pádua Lúcio K. Araújo C.M. de Araújo G.R. de Amorim Miranda P.H. Carneiro A.C.A. de Castro Ribeiro É.M. de Melo Silva B. de Lima W.G. Costa D.C. Baccharis trimera protects against ethanol induced hepatotoxicity in vitro and in vivo. J. Ethnopharmacol. 2018 215 1 13 10.1016/j.jep.2017.12.043 29289796
    [Google Scholar]
  99. Qiu P. Dong Y. Li B. Kang X. Gu C. Zhu T. Luo Y. Pang M. Du W. Ge W. Dihydromyricetin modulates p62 and autophagy crosstalk with the Keap-1/Nrf2 pathway to alleviate ethanol-induced hepatic injury. Toxicol. Lett. 2017 274 31 41 10.1016/j.toxlet.2017.04.009 28419832
    [Google Scholar]
  100. Bai D. Sun T. Lu F. Shen Y. Zhang Y. Zhang B. Yu G. Li H. Hao J. Eupatilin suppresses OVA-induced asthma by inhibiting NF-κB and MAPK and activating Nrf2 signaling pathways in mice. Int. J. Mol. Sci. 2022 23 3 1582 10.3390/ijms23031582 35163503
    [Google Scholar]
  101. Zeng H. Wang Y. Gu Y. Wang J. Zhang H. Gao H. Jin Q. Zhao L. Polydatin attenuates reactive oxygen species-induced airway remodeling by promoting Nrf2-mediated antioxidant signaling in asthma mouse model. Life Sci. 2019 218 25 30 10.1016/j.lfs.2018.08.013 30092299
    [Google Scholar]
  102. Lee B.H. Hsu W.H. Chang Y.Y. Kuo H.F. Hsu Y.W. Pan T.M. Ankaflavin: A natural novel PPARγ agonist upregulates Nrf2 to attenuate methylglyoxal-induced diabetes in vivo. Free Radic. Biol. Med. 2012 53 11 2008 2016 10.1016/j.freeradbiomed.2012.09.025 23022408
    [Google Scholar]
/content/journals/cmccnsa/10.2174/0118715249377844250806052840
Loading
Shielding the Brain: Nrf2-ARE Pathway as a Therapeutic Focus in Epilepsy
Bentham Science Publishers ; https://doi.org/10.2174/0118715249377844250806052840
/content/journals/cmccnsa/10.2174/0118715249377844250806052840
/content/journals/cmccnsa/10.2174/0118715249377844250806052840
Loading

Data & Media loading...


  • Article Type:     Review Article
Keywords: Nrf2-ARE pathway ; neuroprotection ; oxidative stress ; Nrf2 activators ; Epilepsy ; antioxidant response elements
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test