艾地苯醌在帕金森病中的应用进展Application of idebenone in Parkinson's disease
徐朝辉;陈瑛;肖倩;梁彪;陈珍;李国毅;程记伟;赵卿;
摘要(Abstract):
帕金森病是常见的神经系统退行性疾病,线粒体功能障碍是帕金森病发病中的一个重要环节。艾地苯醌是一种线粒体靶向药物,具有较强的抗氧化能力,能有效改善线粒体功能。本文从线粒体功能障碍与帕金森病的关系、艾地苯醌药理机制、艾地苯醌在帕金森病中的应用进行综述,旨在深入探讨艾地苯醌在帕金森病中的应用价值及其潜在的疾病修饰作用。
关键词(KeyWords): 帕金森病;艾地苯醌;线粒体功能障碍;氧化应激;多巴胺神经元
基金项目(Foundation): 2019年度上海市普陀区卫生健康系统临床特色专病建设项目(编号:2019tszb02);; 普陀区卫生健康系统科技创新项目(编号:ptkwws202009);; 上海市中医医院第二届中医传承项目(编号:沪中医人【2020】2号)
作者(Authors): 徐朝辉;陈瑛;肖倩;梁彪;陈珍;李国毅;程记伟;赵卿;
参考文献(References):
- [1]中华医学会神经病学分会帕金森病及运动障碍学组,中国医师协会神经内科医师分会帕金森病及运动障碍学组.中国帕金森病治疗指南(第四版)[J].中华神经科杂志,2020,53(12):973-986. DOI:10.3760/cma.j.cn113694-20200331-00233.
- [2] LI G,MA J,CUI S,et al. Parkinson’s disease in China:a forty-year growing track of bedside work[J]. Transl Neurodegener,2019,8(1):22.DOI:10.1186/s40035-019-0162-z.
- [3] CHEN W,XIAO Q,SHAO M,et al. Prevalence of wearing-off and dyskinesia among the patients with Parkinson’s disease on levodopa therapy:a multi-center registry survey in China's mainland[J]. Transl Neurodegener,2014,3(1):26. DOI:10.1186/2047-9158-3-26.
- [4] DIRNAGL U,BECKER K,MEISEL A. Neuroinflammation in Parkinson’s disease:a target for neuroprotection?[J]. Lancet Neurol,2009,8(4):382-397. DOI:10.1016/S1474-4422(09)70062-6.
- [5] BAKY N,ZAIDI Z F,FATANI A J,et al. Nitric oxide pros and cons:The role of L-arginine,a nitric oxide precursor,and idebenone,a coenzyme-Q analogue in ameliorating cerebral hypoxia in rat[J]. Brain Res Bull,2010,83(1/2):49-56. DOI:10.1016/j.brainresbull.2010.07.004.
- [6] LANGSTON J,BALLARD P,TETRUD J,et al.Chronic Parkinsonism in humans due to a product of meperidine-analog synthesis[J]. Science,1983,219(4587):979-980. DOI:10.1126/science.6823561.
- [7] NICKLAS W,VYAS I,HEIKKILA R E. Inhibition of NADH-linked oxidation in brain mitochondria by 1-methyl-4-phenyl-pyridine,a metabolite of the neurotoxin,1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine[J]. Life Sci,1985,36(26):2503-2508. DOI:10.1016/0024-3205(85)90146-8.
- [8] TRIMMER P A,SWERDLOW R H,PARKS J K,et al. Abnormal mitochondrial morphology in sporadic Parkinson’s and Alzheimer’s disease cybrid cell lines[J]. Exp Neurol,2000,162(1):37-50. DOI:10.1006/exnr.2000.7333.
- [9] LUO Y,HOFFER A,HOFFER B,et al. Mitochondria:A therapeutic target for Parkinson’s disease?[J]. Int J Mol Sci,2015,16(9):20704-20730. DOI:10.3390/ijms160920704.
- [10] KOENE S,DE LAAT P,VAN TIENOVEN D H,et al. Serum GDF15 levels correlate to mitochondrial disease severity and myocardial strain,but not to disease progression in adult m.3243A>G carriers[J].JIMD Rep,2015,24:69-81. DOI:10.1007/8904_2015_436.
- [11] YAO X M,WANG D,ZHANG L,et al. Serum growth differentiation factor 15 in Parkinson’s disease[J].Neurodegener Dis,2017,17(6):251-260. DOI:10.1159/000477349.
- [12] BRAAK H,GHEBREMEDHIN E,RüB U,et al. Stages in the development of Parkinson’s disease-related pathology[J]. Cell Tissue Res,2004,318(1):121-134. DOI:10.1007/s00441-004-0956-9
- [13] DE VOS K J,GRIERSON A J,ACKERLEY S,et al. Role of axonal transport in neurodegenerative diseases[J]. Annu Rev Neurosci,2008,31(1):151-173. DOI:10.1146/annurev.neuro.31.061307.090711.
- [14] LARSEN S B,HANSS Z,KRüGER R. The genetic architecture of mitochondrial dysfunction in Parkinson’s disease[J]. Cell Tissue Res,2018, 373(1):21-37. DOI:10.1007/s00441-017-2768-8.
- [15] PICKRELL A,YOULE R. The roles of PINK1,parkin,and mitochondrial fidelity in Parkinson’s disease[J]. Neuron,2015,85(2):257-273. DOI:10.1016/j.neuron.2014.12.007.
- [16] ABELIOVICH A. Parkinson’s disease:Mitochondrial damage control[J]. Nature,2010,463(7282):744-745. DOI:10.1038/463744a.
- [17] MAITA C,MAITA H,IGUCHI-ARIGA S M,et al. Monomer DJ-1 and its N-terminal sequence are necessary for mitochondrial localization of DJ-1 mutants[J]. PLoS One,2013,8(1):e54087. DOI:10.1371/journal.pone.0054087.
- [18] DOLGACHEVA L P,BEREZHNOV A V,FEDOTOVA E I,et al. Role of DJ-1 in the mechanism of pathogenesis of Parkinson’s disease[J]. J Bioenerg Biomembr,2019,51(3):175-188. DOI:10.1007/s10863-019-09798-4.
- [19] NAKAMURA K,NEMANI V M,WALLENDER E K,et al. Optical reporters for the conformation ofα-synuclein reveal a specific interaction with mitochondria[J]. J Neurosci,2008,28(47):12305-12317. DOI:10.1523/JNEUROSCI.3088-08.2008.
- [20] ROCHA E M,DE MIRANDA B,SANDERS L H. Alpha-synuclein:Pathology,mitochondrial dysfunction and neuroinflammation in Parkinson’s disease[J]. Neurobiol Dis,2018,109(Pt B):249-257. DOI:10.1016/j.nbd.2017.04.004.
- [21] MOISOI N,KLUPSCH K,FEDELE V,et al.Mitochondrial dysfunction triggered by loss of HtrA2 results in the activation of a brain-specific transcriptional stress response[J]. Cell Death Differ,2009,16(3):449-464. DOI:10.1038/cdd.2008.166.
- [22] ITOH K,NAKAMURA K,IIJIMA M,et al. Mitochondrial dynamics in neurodegeneration[J].Trends Cell Biol,2013,23(2):64-71. DOI:10.1016/j.tcb.2012.10.006.
- [23] BHURTEL S,KATILA N,SRIVASTAV S,et al. Mechanistic comparison between MPTP and rotenone neurotoxicity in mice[J]. NeuroToxicology,2019,71:113-121. DOI:10.1016/j.neuro.2018.12.009.
- [24] CLEETER M W,COOPER J M,DARLEY-USMAR V M,et al. Reversible inhibition of cytochrome c oxidase,the terminal enzyme of the mitochondrial respiratory chain,by nitric oxide.Implications for neurodegenerative diseases[J]. Febs Lett,1994,345(1):50-54. DOI:10.1016/0014-5793(94)00424-2.
- [25] RICHARDSON J R,YU Q,SHERER T B,et al. Paraquat neurotoxicity is distinct from that of MPTP and rotenone[J]. Toxicol Sci,2005,88(1):193-201. DOI:10.1093/toxsci/kfi304.
- [26] TANNER C M,KAMEL F,ROSS G W,et al.Rotenone,Paraquat,and Parkinson’s disease[J]. Environ Health Perspect,2011,119(6):866-872. DOI:10.1289/ehp.1002839.
- [27] CHENG P,YU J,HUANG W,et al. Dietary intake of iron,zinc,copper,and risk of Parkinson’s disease:a meta-analysis[J]. Neurol Sci,2015,36(12):2269-2275. DOI:10.1007/s10072-015-2349-0.
- [28] BECKER C,BRAY-FRENCH K,DREWE J.Pharmacokinetic evaluation of idebenone[J].Expert Opin Drug Metab Toxicol,2010,6(11):1437-1444. DOI:10.1517/17425255.2010.530656.
- [29] MICHAEL E,BARBARA H E,HOLGER D,et al. Features of idebenone and related short-chain quinones that rescue ATP levels under conditions of impaired mitochondrial complex I[J]. PLoS One,2012,7(4):e36153.DOI:10.1371/journal.pone.0036153.
- [30] PERRY J B,DAVIS G N,ALLEN M E,et al.Cardioprotective effects of idebenone do not involve ROS scavenging:Evidence for mitochondrial complex I bypass in ischemia/reperfusion injury[J]. J Mol Cell Cardiol,2019,135:160-171. DOI:10.1016/j.yjmcc.2019.08.010.
- [31] CARDOSO S M,PEREIRA C,OLIVEIRA C R. The protective effect of vitamin E,idebenone and reduced glutathione on free radical mediated injury in rat brain synaptosomes[J].Biochem Biophys Res Commun,1998,246(3):703-710. DOI:10.1006/bbrc.1998.8563.
- [32] DELGADO-BUENROSTRO N L,FREYREFONSECA V,CUELLAR C,et al. Decrease in respiratory function and electron transport chain induced by airborne particulate matter(PM10)exposure in lung mitochondria[J].Toxicol Pathol,2013,41(4):628-638. DOI:10.1177/0192623312463784.
- [33] YI C,LIN Y W,WANG S J. Idebenone inhibition of glutamate release from rat cerebral cortex nerve endings by suppression of voltage-dependent calcium influx and protein kinase A[J]. Naunyn Schmiedebergs Arch Pharmacol,2011,384(1):59-70. DOI:10.1007/s00210-011-0630-1.
- [34] GARRIDO-MARAVER J,CORDERO M D,OROPESA-AVILA M,et al. Clinical applications of coenzyme Q10[J]. Front Biosci,2014,19:619-633. DOI:10.2741/4231.
- [35] ORSUCCI D,MANCUSO M,IENCO E C,et al. Targeting mitochondrial dysfunction and neurodegeneration by means of coenzyme Q10and its analogues[J]. Curr Med Chem,2011,18(26):4053-4064. DOI:10.2174/092986711796957257.
- [36] BHAGAVAN H N,CHOPRA R K. Coenzyme Q10:Absorption,tissue uptake,metabolism and pharmacokinetics[J]. Free Radic Res,2006,40(5):445-453. DOI:10.1080/10715760600617843.
- [37] GUEVEN N,WOOLLEY K,SMITH J. Border between natural product and drug:Comparison of the related benzoquinones idebenone and coenzyme Q10[J]. Redox Biol,2015,4:289-295. DOI:10.1016/j.redox.2015.01.009.
- [38] KING M S,SHARPLEY M S,HIRST J. Reduction of hydrophilic ubiquinones by the flavin in mitochondrial NADH:Ubiquinone oxidoreductase(Complex I)and production of reactive oxygen species[J]. Biochemistry,2009,48(9):2053-2062. DOI:10.1021/bi802282h.
- [39] HAEFELI R H,MICHAEL E,GEMPERLI A C,et al. NQO1-dependent redox cycling of idebenone:Effects on cellular redox potential and energy levels[J]. PLoS One,2011,6(3):e17963. DOI:10.1371/journal.pone.0017963.
- [40] RAUCHOVáH,VOKURKOVáM,DRAHOTA Z. Idebenone-induced recovery of glycerol-3-phosphate and succinate oxidation inhibited by digitonin[J]. Physiol Res,2012,61(3):259. DOI:10.33549/physiolres.932318.
- [41] MCDANIEL D H,NEUDECKER B A,DINARDO J C,et al. Idebenone:a new antioxidantPart I. Relative assessment of oxidative stress protection capacity compared to commonly known antioxidants[J]. J Cosmet Dermatol,2005,4(1):10-17. DOI:10.1111/j.1473-2165.2005.00152.x.
- [42] AVC B,GüNAYDN C,GüVEN T,et al. Idebenone ameliorates rotenone-induced Parkinson’s disease in rats through decreasing lipid peroxidation[J]. Neurochem Res,2021,46(3):513-522. DOI:10.1007/s11064-020-03186-w.
- [43] GERHARDT E,GR?BER S,SZEGO E M,et al. Idebenone and resveratrol extend lifespan and improve motor function of HtrA2 knockout mice[J]. PLoS One,2011,6(12):e28855.DOI:10.1371/journal.pone.0028855.
- [44]闫俊强,刘安然,黄家瑞,等.艾地苯醌对帕金森病模型小鼠行为学及脑组织线粒体自噬水平的影响[J].中华行为医学与脑科学杂志,2021,30(1):15-21. DOI:10.3760/cma.j.cn371468-20201014-01792.
- [45]盛泳佳,杨毅,李文燕,等.艾地苯醌对帕金森病小鼠行为学改善的作用及其机制[J].中国现代应用药学,2019,36(6):46-51. DOI:10.13748/j.cnki.issn1007-7693.2019.06.008.
- [46] SCHAPANSKY J,NARDOZZI J D,LAVOIE M J. The complex relationships between microglia,alpha-synuclein,and LRRK2 in Parkinson’s disease[J]. Neuroscience,2015,(302):74-88. DOI:10.1016/j.neuroscience.2014.09.049.
- [47] YAN A,LIU Z,SONG L,et al. Idebenone alleviates neuroinflammation and modulates microglial polarization in LPS-stimulated BV2Cells and MPTP-induced Parkinson’s disease mice[J]. Front Cell Neurosci,2019,12:529.DOI:10.3389/fncel.2018.00529.
- [48]刘瑜.艾地苯醌联合常规药物治疗帕金森病疗效的临床观察[J].中国医药指南,2020,18(29):97-98. DOI:10.15912/j.cnki.gocm.2020.29.046.
- [49]兰晓艳,温德树.艾地苯醌联合多巴丝肼对帕金森病伴认知功能障碍患者认知功能和生活能力的影响[J].中国医院用药评价与分析,2019,19(10):1202-1205. DOI:10.14009/j.issn.1672-2124.2019.10.014.
- [50]夏秋怡,徐茂青,霍青.艾地苯醌结合美多芭对帕金森患者的疗效、步态及精神状态的影响[J].卒中与神经疾病,2020,27(5):627-630. DOI:10.3969/j.issn.1007-0478.2020.05.015.
- [51]陈烈冉,张保朝,付国惠.艾地苯醌联合多巴丝肼治疗帕金森病的效果及对患者脑脊液相关炎性因子的影响[J].中国实用医刊,2020,47(6):101-104. DOI:10.3760/cma.j.cn115689-20191120-08200.
- [52]康蓓,慕生枝,李妮妮,等.艾地苯醌联合多巴丝肼治疗帕金森病的疗效及对氧化应激因子的影响[J].山西医药杂志,2019,48(16):1958-1960. DOI:10.3969/j.issn.0253-9926.2019.16.003.
- [53]慕英.艾地苯醌联合多巴丝肼治疗帕金森病的效果[J].河南医学研究,2020,29(35):6642-6644. DOI:10.3969/j.issn.1004-437X.2020.35.046.
- [54]张晓韬,何天齐,朱梅佳,等.艾地苯醌联合治疗帕金森病疗效的临床观察[J].山东大学学报(医学版),2019,57(4):34-41. DOI:10.6040/j.issn.1671-7554.0.2018.1301.
- [55]徐珍.艾地苯醌辅助治疗帕金森病疗效观察[J].临床合理用药杂志,2020,13(14):35-37. DOI:CNKI:SUN:PLHY.0.2020-14-018.
- [56]于凌,孔敏,梁辉.艾地苯醌对早期帕金森病的疗效观察[J].河北医药,2019,41(11):1689-1691;1695. DOI:10.3969/j.issn.1002-7386.2019.11.021
- [57] YATSUGA S,FUJITA Y,ISHII A,et al. Growth differentiation factor 15 as a useful biomarker for mitochondrial disorders[J]. Ann Neurol,2015,78(5):814-823. DOI:10.1002/ana.24506.
- [58]黄骥,阳军,欧阳娟,等.艾地苯醌联合多巴丝肼治疗帕金森病的临床研究[J].药物评价研究,2020,43(12):2501-2504. DOI:10.7501/j.issn.1674-6376.2020.12.028.
- [59]杨硕,赵丹鹏,李琳,等.艾地苯醌对帕金森患者额叶磁共振波谱成像的影响[J].中国合理用药探索,2019,16(2):124-126;130. DOI:10.3969/j.issn.2096-3327.2019.2.035.
- [60] ALONSO B D C,HIDALGO-TOBóN S S,MENéNDEZ-GONZáLEZ M,et al. Magnetic resonance techniques applied to the diagnosis and treatment of Parkinson’s disease[J].Front Neurol,2015,6:146. DOI:10.3389/fneur.2015.00146.
- [61] BECKER S,B?UMER A,MAETZLER W,et al. Assessment of cognitive-driven activity of daily living impairment in non-demented Parkinson’s patients[J]. J Neuropsychol,2020,14(Pt.1):69-84. DOI:10.1111/jnp.12173.
- [62]马秀娟,朱宁,朱洪山,等.艾地苯醌治疗帕金森病轻度认知障碍的临床疗效观察[J].世界最新医学信息文摘,2020,20(16):138-139;141. DOI:10.19613/j.cnki.1671-3141.2020.16.078.