线粒体：神经退行性变的一个治疗靶点。
Mitochondria: a therapeutic target in neurodegeneration.
作者信息
Moreira Paula I, Zhu Xiongwei, Wang Xinglong, Lee Hyoung-Gon, Nunomura Akihiko, Petersen Robert B, Perry George, Smith Mark A
机构信息
Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.
出版信息
Biochim Biophys Acta. 2010 Jan;1802(1):212-20. doi: 10.1016/j.bbadis.2009.10.007. Epub 2009 Oct 21.
Abstract
Mitochondrial dysfunction has long been associated with neurodegenerative disease. Therefore, mitochondrial protective agents represent a unique direction for the development of drug candidates that can modify the pathogenesis of neurodegeneration. This review discusses evidence showing that mitochondrial dysfunction has a central role in the pathogenesis of Alzheimer's, Parkinson's and Huntington's diseases and amyotrophic lateral sclerosis. We also debate the potential therapeutic efficacy of metabolic antioxidants, mitochondria-directed antioxidants and Szeto-Schiller (SS) peptides. Since these compounds preferentially target mitochondria, a major source of oxidative damage, they are promising therapeutic candidates for neurodegenerative diseases. Furthermore, we will briefly discuss the novel action of the antihistamine drug Dimebon on mitochondria.
摘要
长期以来，线粒体功能障碍一直与神经退行性疾病相关。因此，线粒体保护剂代表了一类独特的候选药物开发方向，这类药物可以改变神经退行性变的发病机制。本综述讨论了相关证据，这些证据表明线粒体功能障碍在阿尔茨海默病、帕金森病、亨廷顿病和肌萎缩侧索硬化症的发病机制中起核心作用。我们还对代谢抗氧化剂、线粒体靶向抗氧化剂和泽托-席勒（SS）肽的潜在治疗效果进行了讨论。由于这些化合物优先靶向氧化损伤的主要来源——线粒体，它们有望成为治疗神经退行性疾病的候选药物。此外，我们将简要讨论抗组胺药二甲金刚胺对线粒体的新作用。
相似文献
1
Mitochondria: a therapeutic target in neurodegeneration.线粒体：神经退行性变的一个治疗靶点。
Biochim Biophys Acta. 2010 Jan;1802(1):212-20. doi: 10.1016/j.bbadis.2009.10.007. Epub 2009 Oct 21.
2
Mitochondrial Medicine: A Promising Therapeutic Option Against Various Neurodegenerative Disorders.线粒体医学：对抗多种神经退行性疾病的有前途的治疗选择。
Curr Neuropharmacol. 2023;21(5):1165-1183. doi: 10.2174/1570159X20666220830112408.
3
Mitochondrial abnormalities in Parkinson's disease and Alzheimer's disease: can mitochondria be targeted therapeutically?帕金森病和阿尔茨海默病中的线粒体异常：线粒体可以作为治疗靶点吗？
Biochem Soc Trans. 2018 Aug 20;46(4):891-909. doi: 10.1042/BST20170501. Epub 2018 Jul 19.
4
Mitochondrial dysfunction and oxidative stress in Alzheimer's disease, and Parkinson's disease, Huntington's disease and Amyotrophic Lateral Sclerosis -An updated review.阿尔茨海默病、帕金森病、亨廷顿病和肌萎缩侧索硬化症中的线粒体功能障碍和氧化应激——最新综述。
Mitochondrion. 2023 Jul;71:83-92. doi: 10.1016/j.mito.2023.05.007. Epub 2023 Jun 1.
5
PPARγ as a therapeutic target to rescue mitochondrial function in neurological disease.过氧化物酶体增殖物激活受体γ作为挽救神经疾病中线粒体功能的治疗靶点。
Free Radic Biol Med. 2016 Nov;100:153-163. doi: 10.1016/j.freeradbiomed.2016.06.023. Epub 2016 Jun 25.
6
Mitochondria and neurodegeneration.线粒体与神经退行性变
Biosci Rep. 2007 Jun;27(1-3):87-104. doi: 10.1007/s10540-007-9038-z.
7
Small molecules as therapeutic drugs for Alzheimer's disease.小分子作为治疗阿尔茨海默病的药物。
Mol Cell Neurosci. 2019 Apr;96:47-62. doi: 10.1016/j.mcn.2019.03.001. Epub 2019 Mar 12.
8
Mitochondrial Dysfunctions: A Red Thread across Neurodegenerative Diseases.线粒体功能障碍：神经退行性疾病的共同线索
Int J Mol Sci. 2020 May 25;21(10):3719. doi: 10.3390/ijms21103719.
9
Oxidative stress, mitochondrial dysfunction and cellular stress response in Friedreich's ataxia.弗里德赖希共济失调中的氧化应激、线粒体功能障碍和细胞应激反应
J Neurol Sci. 2005 Jun 15;233(1-2):145-62. doi: 10.1016/j.jns.2005.03.012.
10
Mitochondrial dysfunction and oxidative damage in Alzheimer's and Parkinson's diseases and coenzyme Q10 as a potential treatment.阿尔茨海默病和帕金森病中的线粒体功能障碍与氧化损伤以及辅酶Q10作为一种潜在治疗方法
J Bioenerg Biomembr. 2004 Aug;36(4):381-6. doi: 10.1023/B:JOBB.0000041772.74810.92.
引用本文的文献
1
Neurotoxicological Effects of Some Mycotoxins on Humans Health and Methods of Neuroprotection.某些霉菌毒素对人类健康的神经毒理学影响及神经保护方法
Toxins (Basel). 2025 Jan 6;17(1):24. doi: 10.3390/toxins17010024.
2
Multi-omics characterization of improved cognitive functions in Parkinson's disease patients after the combined metabolic activator treatment: a randomized, double-blinded, placebo-controlled phase II trial.帕金森病患者联合代谢激活剂治疗后认知功能改善的多组学特征：一项随机、双盲、安慰剂对照的II期试验。
Brain Commun. 2025 Jan 6;7(1):fcae478. doi: 10.1093/braincomms/fcae478. eCollection 2025.
3
Effect of Dietary Ketosis and Nicotinamide Riboside on Hippocampal Krebs Cycle Intermediates and Mitochondrial Energetics in a DNA Repair-Deficient 3xTg/POLβ Alzheimer Disease Mouse Model.饮食性酮症和烟酰胺核糖对DNA修复缺陷的3xTg/POLβ阿尔茨海默病小鼠模型海马中三羧酸循环中间体和线粒体能量代谢的影响。
J Neurochem. 2025 Jan;169(1):e16295. doi: 10.1111/jnc.16295.
4
Mitochondria-Targeted Antioxidant MitoQ Improves In Vitro Maturation and Subsequent Embryonic Development from Culled Cows.线粒体靶向抗氧化剂MitoQ改善淘汰奶牛的体外成熟及后续胚胎发育
Animals (Basel). 2024 Oct 11;14(20):2929. doi: 10.3390/ani14202929.
5
Molecular mechanisms of mitochondrial homeostasis regulation in neurons and possible therapeutic approaches for Alzheimer's disease.神经元中线粒体稳态调节的分子机制及阿尔茨海默病的潜在治疗方法。
Heliyon. 2024 Aug 17;10(17):e36470. doi: 10.1016/j.heliyon.2024.e36470. eCollection 2024 Sep 15.
6
The Effect of Neuronal CoQ Deficiency and Mitochondrial Dysfunction on a Rotenone-Induced Neuronal Cell Model of Parkinson's Disease.神经元辅酶 Q 缺乏和线粒体功能障碍对鱼藤酮诱导的帕金森病神经元细胞模型的影响。
Int J Mol Sci. 2024 Jun 16;25(12):6622. doi: 10.3390/ijms25126622.
7
Alleviating Neurodegenerative Diseases Associated with Mitochondrial Defects by Therapeutic Biomolecules.治疗性生物分子缓解与线粒体缺陷相关的神经退行性疾病。
Curr Top Med Chem. 2024;24(16):1377-1407. doi: 10.2174/0115680266299148240329062647.
8
Calcium Modulating Effect of Polycyclic Cages: A Suitable Therapeutic Approach Against Excitotoxic-induced Neurodegeneration.多环笼状化合物的钙调节作用：一种针对兴奋毒性诱导的神经退行性变的合适治疗方法。
Mini Rev Med Chem. 2024;24(13):1277-1292. doi: 10.2174/0113895575273868231128104121.
9
Anti oxidative/neuro-inflammation properties of on rotenone induced stress in rat brain.[物质名称]对鱼藤酮诱导的大鼠脑应激的抗氧化/神经炎症特性
Bioinformation. 2023 Jun 30;19(6):729-738. doi: 10.6026/97320630019729. eCollection 2023.
10
The functional role of Higd1a in mitochondrial homeostasis and in multiple disease processes.Higd1a在线粒体稳态及多种疾病进程中的功能作用。
Genes Dis. 2022 Apr 22;10(5):1833-1845. doi: 10.1016/j.gendis.2022.03.018. eCollection 2023 Sep.
本文引用的文献
1
Involvment of cytosolic and mitochondrial GSK-3beta in mitochondrial dysfunction and neuronal cell death of MPTP/MPP-treated neurons.胞质和线粒体GSK-3β参与MPTP/MPP处理的神经元的线粒体功能障碍和神经元细胞死亡。
PLoS One. 2009;4(5):e5491. doi: 10.1371/journal.pone.0005491. Epub 2009 May 11.
2
Conversion to dementia in mild cognitive impairment is associated with decline of N-actylaspartate and creatine as revealed by magnetic resonance spectroscopy.磁共振波谱显示，轻度认知障碍向痴呆的转化与N-乙酰天门冬氨酸和肌酸的减少有关。
Psychiatry Res. 2009 Jul 15;173(1):1-7. doi: 10.1016/j.pscychresns.2008.07.015. Epub 2009 May 9.
3
An integrative view of the role of oxidative stress, mitochondria and insulin in Alzheimer's disease.氧化应激、线粒体与胰岛素在阿尔茨海默病中作用的综合观点
J Alzheimers Dis. 2009;16(4):741-61. doi: 10.3233/JAD-2009-0972.
4
S-nitrosylation of Drp1 mediates beta-amyloid-related mitochondrial fission and neuronal injury.动力相关蛋白1（Drp1）的S-亚硝基化介导β-淀粉样蛋白相关的线粒体分裂和神经元损伤。
Science. 2009 Apr 3;324(5923):102-5. doi: 10.1126/science.1171091.
5
The effect of acetyl-L-carnitine and R-alpha-lipoic acid treatment in ApoE4 mouse as a model of human Alzheimer's disease.以ApoE4小鼠作为人类阿尔茨海默病模型，研究乙酰-L-肉碱和R-α-硫辛酸治疗的效果。
J Neurol Sci. 2009 Aug 15;283(1-2):199-206. doi: 10.1016/j.jns.2009.03.002. Epub 2009 Apr 1.
6
PINK1 defect causes mitochondrial dysfunction, proteasomal deficit and alpha-synuclein aggregation in cell culture models of Parkinson's disease.在帕金森病的细胞培养模型中，PINK1缺陷会导致线粒体功能障碍、蛋白酶体缺陷和α-突触核蛋白聚集。
PLoS One. 2009;4(2):e4597. doi: 10.1371/journal.pone.0004597. Epub 2009 Feb 26.
7
Mitochondria targeted peptides protect against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine neurotoxicity.线粒体靶向肽可预防 1-甲基-4-苯基-1,2,3,6-四氢吡啶神经毒性。
Antioxid Redox Signal. 2009 Sep;11(9):2095-104. doi: 10.1089/ars.2009.2445.
8
Rotenone damages striatal organotypic slice culture.鱼藤酮会损害纹状体器官型切片培养物。
Ann N Y Acad Sci. 2008 Dec;1148:530-5. doi: 10.1196/annals.1410.009.
9
Long-term creatine supplementation is safe in aged patients with Parkinson disease.长期补充肌酸对老年帕金森病患者是安全的。
Nutr Res. 2008 Mar;28(3):172-8. doi: 10.1016/j.nutres.2008.01.001.
10
Cu/Zn superoxide dismutase typical for familial amyotrophic lateral sclerosis increases the vulnerability of mitochondria and perturbs Ca2+ homeostasis in SOD1G93A mice.家族性肌萎缩侧索硬化症典型的铜/锌超氧化物歧化酶增加了SOD1G93A小鼠线粒体的易损性并扰乱了钙离子稳态。
Mol Pharmacol. 2009 Mar;75(3):478-89. doi: 10.1124/mol.108.050831. Epub 2008 Dec 5.
Zotero 插件