Research progress on the correlation between mitochondrial pathway and epilepsy_Journal of Epilepsy

Authors：

LV Jiahua ¹ , LIU Ruihan ² ,  KONG Qingxia ³

1. Clinical Medical College, Jining Medical University, Jining 272000, China;
2. Department of Pediatrics, Affiliated Hospital of Jining Medical University, Jining 272000, China;
3. Department of Neurology, Affiliated Hospital of Jining Medical University, Jining 272000, China;

Corresponding author：

KONG Qingxia, Email: kxdqy8@sohu.com

Keywords：

Epilepsy; Mitochondria; Pathogenesis; Adenosine-triphosphate; Coenzyme Q10

DOI：

10.7507/2096-0247.202303001

Video：

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Epilepsy is a complex disease spectrum, because of long-term recurrent seizures and seriously affect the quality of life of patients, it is of great significance to explore the pathogenesis of epilepsy and actively seek new therapeutic targets. In this paper, the pathogenesis of epilepsy related to mitochondrial pathway was discussed from the aspects of energy depletion, oxidative stress damage, impaired calcium homeostasis, increased glutamic acid release, mitochondrial DNA mutation, Coenzyme Q10 deficiency, abnormal mitochondrial movement and change, and relevant therapeutic ideas were proposed. This paper shows that mitochondrial function affects the onset of epilepsy from various ways. Further understanding of the relationship between mitochondria and the onset of epilepsy is beneficial to find new therapeutic targets and develop new therapies beyond the control of epilepsy.

Citation： LV Jiahua, LIU Ruihan, KONG Qingxia. Research progress on the correlation between mitochondrial pathway and epilepsy. Journal of Epilepsy, 2023, 9(4): 321-325. doi: 10.7507/2096-0247.202303001 Copy

1.	Thijs RD, Surges R, O'Brien TJ, et al. Epilepsy in adults. Lancet, 2019, 393(10172): 689-701.
2.	Klein P, Dingledine R, Aronica E, et al. Commonalities in epileptogenic processes from different acute brain insults: Do they translate? Epilepsia, 2018, 59（1）: 37-66.
3.	Simonato M. Epilepsy an update on disease mechanisms: the potential role of MicroRNAs. Frontiers in Neurology, 2018, 9: 176.
4.	Vezzani A, Balosso S, Ravizza T. Neuroinflammatory pathways as treatment targets and biomarkers in epilepsy. Nature Reviews Neurology, 2019, 15(8): 459-472.
5.	Jerath NU, Shy ME. Asymmetric ataxia, depression, memory loss, epilepsy, and axonal neuropathy associated with a heterozygous dna polymerase gamma variant of uncertain significance, c1370G>a (R457Q). Journal of Neuromuscular Diseases, 2018, 5(1): 99-104.
6.	Li S, Sheng ZH. Energy matters: presynaptic metabolism and the maintenance of synaptic transmission. Nature Reviews Neuroscience, 2022, 23(1): 4-22.
7.	刘楠, 邢岩, 张洁. 1例NDUFA1基因突变所致Leigh综合征及家系报道. 神经损伤与功能重建, 2022, 17(6): 369-371.
8.	Martin-Mcgill K, Bresnahan R, Levy R, et al. Ketogenic diets for drug-resistant epilepsy. The Cochrane Database of Systematic Reviews, 2020, 6(6): CD001903.
9.	De Souza Neves G, Dos Santos Lunardi M, Papini Gabiatti M, et al. Cardiometabolic risk and effectiveness of the modified atkins ketogenic diet for adult patients with pharmacoresistant epilepsies in a middle-incomecountry. Epilepsy Research, 2020, 160: 106280.
10.	包钟元, 季晶. 铁死亡在颅脑外伤中的研究进展. 南京医科大学学报(自然科学版), 2022, 42(2): 270-278.
11.	Rho JM, Boison D. The metabolic basis of epilepsy. Nature Reviews Neurology, 2022, 18(6): 333-347.
12.	Srivastava NK, Mukherjee S, Sharma R, et al. Altered lipid metabolism in post-traumatic epileptic rat model: one proposed pathway. Molecular Biology Reports, 2019, 46(2): 1757-1773.
13.	Goyal A, Gopika S, Agrawal N. Basic leucine zipper protein nuclear factor erythroid 2-related factor 2 as a potential therapeutic target in brain related disorders. Protein and peptide letters, 2022, 29(8): 676-691.
14.	Liu L, Zhang K, Sandoval H, et al. Glial lipid droplets and ROS induced by mitochondrial defects promote neurodegeneration. Cell, 2015, 160(1-2): 177-190.
15.	Yang N, Guan QW, Chen FH, et al. Antioxidants targeting mitochondrial oxidative stress: promising neuroprotectants for epilepsy. Oxidative Medicine and Cellular Longevity, 2020, 2020: 6687185.
16.	李传朋, 高颖, 高永红, 等. 脑缺血再灌注损伤中钙超载相关通路研究进展. 中国医药导报, 2022, 19(12): 46-50.
17.	Cappuccio G, Pinelli M, Alagia M, et al. Biochemical phenotyping unravels novel metabolic abnormalities and potential biomarkers associated with treatment of GLUT1 deficiency with ketogenic diet. PloS One, 2017, 12(9): e0184022.
18.	Depp C, Bas-Orth C, Schroeder L, et al. Synaptic activity protects neurons against calcium-mediated oxidation and contraction of mitochondria during excitotoxicity. Antioxidants & Redox Signaling, 2018, 29(12): 1109-1124.
19.	符敏峰. 小儿癫痫应用丙戊酸钠结合左乙拉西坦治疗的效果. 吉林医学, 2021, 42(6): 1423-1424.
20.	Yan C, Duanmu X, Zeng L, et al. Mitochondrial DNA: distribution, mutations, and elimination. Cells, 2019, 8(4): 379-379.
21.	孙翀, 陆珺, 奚剑英, 等. 线粒体基因8344A >G突变相关肌阵挛性癫痫伴破碎红纤维-Leigh叠加综合征一例. 中华神经科杂志, 2021, 54(10): 1059-1063.
22.	Finsterer J. Photosensitive epilepsy and polycystic ovary syndrome as manifestations of MERRF. Case Reports in Neurological Medicine, 2020, 2020: 8876272.
23.	李生瑞. 儿童原发性线粒体病相关癫痫的临床/遗传学特征及危险因素分析. 重庆医科大学, 2022, 硕士学位论文.
24.	Wang L, Lu Z, Zhao J, et al. Selective oxidative stress induces dual damage to telomeres and mitochondria in human T cells. Aging Cell, 2021, 20(12): e13513.
25.	Guerrero-Molina MP, Morales-Conejo M, Delmiro A, et al. Elevated glutamate and decreased glutamine levelsin the cerebrospinal fluid of patients with MELAS syndrome. Journal of Neurology, 2022, 269(6): 3238-3248.
26.	Capristo M, Del Dotto V, Tropeano CV, et al. Rapamycin rescues mitochondrial dysfunction in cells carrying the m. 8344A > G mutation in the mitochondrial tRNA. Molecular Medicine (Cambridge, Mass. ), 2022, 28(1): 90-90.
27.	Simani L, Rezaei O, Ryan F, et al. Coenzyme Q10 insufficiency contributes to the duration and frequency of seizures in epileptic patients. Basic and Clinical Neuroscience, 2020, 11(6): 765-771.
28.	Arntsen V, Sand T, Hikmat O, et al. A characteristic occipital epileptiform EEG pattern in ADCK3-related mitochondrial disease. Epileptic Disorders, 2021, 23(2): 281-290.
29.	陈先睿, 许锦平, 姚拥华. 原发性辅酶Q10缺乏7型一例并文献复习. 中华儿科杂志, 2020, 58(11): 928-932.
30.	Bhardwaj M, Kumar A. Neuroprotective mechanism of Coenzyme Q10 (CoQ10) against PTZ induced kindling and associated cognitive dysfunction: possible role of microglia inhibition. Pharmacological Reports, 2016, 68(6): 1301-1311.
31.	Pradhan N, Singh C, Singh A. Coenzyme Q10 a mitochondrial restorer for various brain disorders. Naunyn-Schmiedeberg's Archives of Pharmacology, 2021, 394(11): 2197-2222.
32.	Han Y, Lin Y, Xie N, et al. Impaired mitochondrial biogenesis in hippocampi of rats with chronic seizures. Neuroscience, 2011, 194(1): 234-240.
33.	张海峰. 匹罗卡品致痫小鼠海马神经元线粒体移动变化研究. 郑州大学, 2016, 博士学位论文.
34.	Saotome M, Safiulina D, Szabadkai G, et al. Bidirectional Ca2+-dependent control of mitochondrial dynamicsby the Miro GTPase. Proceedings of the National Academy of Sciences of the United States of America, 2008, 105(52): 20728-20733.
35.	Vig S, Lambooij JM, Zaldumbide A, et al. Endoplasmic reticulum-mitochondria crosstalk and beta-cell destruction in type 1 diabetes. Frontiers in immunology, 2021, 12: 669492.
36.	Varhaug KN, Vedeler CA, Tzoulis C, et al. Multiple sclerosis-a mitochondria-mediated disease? Tidsskrift For Den Norske Laegeforening, 2017, 137（4）: 284-287.

1. Thijs RD, Surges R, O'Brien TJ, et al. Epilepsy in adults. Lancet, 2019, 393(10172): 689-701.
2. Klein P, Dingledine R, Aronica E, et al. Commonalities in epileptogenic processes from different acute brain insults: Do they translate? Epilepsia, 2018, 59（1）: 37-66.
3. Simonato M. Epilepsy an update on disease mechanisms: the potential role of MicroRNAs. Frontiers in Neurology, 2018, 9: 176.
4. Vezzani A, Balosso S, Ravizza T. Neuroinflammatory pathways as treatment targets and biomarkers in epilepsy. Nature Reviews Neurology, 2019, 15(8): 459-472.
5. Jerath NU, Shy ME. Asymmetric ataxia, depression, memory loss, epilepsy, and axonal neuropathy associated with a heterozygous dna polymerase gamma variant of uncertain significance, c1370G>a (R457Q). Journal of Neuromuscular Diseases, 2018, 5(1): 99-104.
6. Li S, Sheng ZH. Energy matters: presynaptic metabolism and the maintenance of synaptic transmission. Nature Reviews Neuroscience, 2022, 23(1): 4-22.
7. 刘楠, 邢岩, 张洁. 1例NDUFA1基因突变所致Leigh综合征及家系报道. 神经损伤与功能重建, 2022, 17(6): 369-371.
8. Martin-Mcgill K, Bresnahan R, Levy R, et al. Ketogenic diets for drug-resistant epilepsy. The Cochrane Database of Systematic Reviews, 2020, 6(6): CD001903.
9. De Souza Neves G, Dos Santos Lunardi M, Papini Gabiatti M, et al. Cardiometabolic risk and effectiveness of the modified atkins ketogenic diet for adult patients with pharmacoresistant epilepsies in a middle-incomecountry. Epilepsy Research, 2020, 160: 106280.
10. 包钟元, 季晶. 铁死亡在颅脑外伤中的研究进展. 南京医科大学学报(自然科学版), 2022, 42(2): 270-278.
11. Rho JM, Boison D. The metabolic basis of epilepsy. Nature Reviews Neurology, 2022, 18(6): 333-347.
12. Srivastava NK, Mukherjee S, Sharma R, et al. Altered lipid metabolism in post-traumatic epileptic rat model: one proposed pathway. Molecular Biology Reports, 2019, 46(2): 1757-1773.
13. Goyal A, Gopika S, Agrawal N. Basic leucine zipper protein nuclear factor erythroid 2-related factor 2 as a potential therapeutic target in brain related disorders. Protein and peptide letters, 2022, 29(8): 676-691.
14. Liu L, Zhang K, Sandoval H, et al. Glial lipid droplets and ROS induced by mitochondrial defects promote neurodegeneration. Cell, 2015, 160(1-2): 177-190.
15. Yang N, Guan QW, Chen FH, et al. Antioxidants targeting mitochondrial oxidative stress: promising neuroprotectants for epilepsy. Oxidative Medicine and Cellular Longevity, 2020, 2020: 6687185.
16. 李传朋, 高颖, 高永红, 等. 脑缺血再灌注损伤中钙超载相关通路研究进展. 中国医药导报, 2022, 19(12): 46-50.
17. Cappuccio G, Pinelli M, Alagia M, et al. Biochemical phenotyping unravels novel metabolic abnormalities and potential biomarkers associated with treatment of GLUT1 deficiency with ketogenic diet. PloS One, 2017, 12(9): e0184022.
18. Depp C, Bas-Orth C, Schroeder L, et al. Synaptic activity protects neurons against calcium-mediated oxidation and contraction of mitochondria during excitotoxicity. Antioxidants & Redox Signaling, 2018, 29(12): 1109-1124.
19. 符敏峰. 小儿癫痫应用丙戊酸钠结合左乙拉西坦治疗的效果. 吉林医学, 2021, 42(6): 1423-1424.
20. Yan C, Duanmu X, Zeng L, et al. Mitochondrial DNA: distribution, mutations, and elimination. Cells, 2019, 8(4): 379-379.
21. 孙翀, 陆珺, 奚剑英, 等. 线粒体基因8344A >G突变相关肌阵挛性癫痫伴破碎红纤维-Leigh叠加综合征一例. 中华神经科杂志, 2021, 54(10): 1059-1063.
22. Finsterer J. Photosensitive epilepsy and polycystic ovary syndrome as manifestations of MERRF. Case Reports in Neurological Medicine, 2020, 2020: 8876272.
23. 李生瑞. 儿童原发性线粒体病相关癫痫的临床/遗传学特征及危险因素分析. 重庆医科大学, 2022, 硕士学位论文.
24. Wang L, Lu Z, Zhao J, et al. Selective oxidative stress induces dual damage to telomeres and mitochondria in human T cells. Aging Cell, 2021, 20(12): e13513.
25. Guerrero-Molina MP, Morales-Conejo M, Delmiro A, et al. Elevated glutamate and decreased glutamine levelsin the cerebrospinal fluid of patients with MELAS syndrome. Journal of Neurology, 2022, 269(6): 3238-3248.
26. Capristo M, Del Dotto V, Tropeano CV, et al. Rapamycin rescues mitochondrial dysfunction in cells carrying the m. 8344A > G mutation in the mitochondrial tRNA. Molecular Medicine (Cambridge, Mass. ), 2022, 28(1): 90-90.
27. Simani L, Rezaei O, Ryan F, et al. Coenzyme Q10 insufficiency contributes to the duration and frequency of seizures in epileptic patients. Basic and Clinical Neuroscience, 2020, 11(6): 765-771.
28. Arntsen V, Sand T, Hikmat O, et al. A characteristic occipital epileptiform EEG pattern in ADCK3-related mitochondrial disease. Epileptic Disorders, 2021, 23(2): 281-290.
29. 陈先睿, 许锦平, 姚拥华. 原发性辅酶Q10缺乏7型一例并文献复习. 中华儿科杂志, 2020, 58(11): 928-932.
30. Bhardwaj M, Kumar A. Neuroprotective mechanism of Coenzyme Q10 (CoQ10) against PTZ induced kindling and associated cognitive dysfunction: possible role of microglia inhibition. Pharmacological Reports, 2016, 68(6): 1301-1311.
31. Pradhan N, Singh C, Singh A. Coenzyme Q10 a mitochondrial restorer for various brain disorders. Naunyn-Schmiedeberg's Archives of Pharmacology, 2021, 394(11): 2197-2222.
32. Han Y, Lin Y, Xie N, et al. Impaired mitochondrial biogenesis in hippocampi of rats with chronic seizures. Neuroscience, 2011, 194(1): 234-240.
33. 张海峰. 匹罗卡品致痫小鼠海马神经元线粒体移动变化研究. 郑州大学, 2016, 博士学位论文.
34. Saotome M, Safiulina D, Szabadkai G, et al. Bidirectional Ca2+-dependent control of mitochondrial dynamicsby the Miro GTPase. Proceedings of the National Academy of Sciences of the United States of America, 2008, 105(52): 20728-20733.
35. Vig S, Lambooij JM, Zaldumbide A, et al. Endoplasmic reticulum-mitochondria crosstalk and beta-cell destruction in type 1 diabetes. Frontiers in immunology, 2021, 12: 669492.
36. Varhaug KN, Vedeler CA, Tzoulis C, et al. Multiple sclerosis-a mitochondria-mediated disease? Tidsskrift For Den Norske Laegeforening, 2017, 137（4）: 284-287.

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