线粒体与神经退行性疾病

摘要/Abstract

摘要： 神经退行性疾病是由神经元和/或其髓鞘的丧失所致，目前该类疾病的病因仍未完全阐明。研究发现，线粒体功能障碍、能量代谢异常, 已成为公认的早期病理现象。本文主要以阿尔茨海默病（Alzheimer’s disease，AD）和帕金森综合症（Parkinson disease，PD）为例，探讨线粒体功能异常在神经退行性疾病发病中的作用，以期为该类疾病诊治和新药研发提供新思路。

关键词: 线粒体, 阿尔茨海默病, 帕金森综合症

Abstract: The neurodegenerative diseases are usually caused by the loss of the neurons and/or their myelin sheath, but the pathogenesis of these diseases are still indeterminate. Studies so far has proved that mitochondrial dysfunction and energy metabolism disorders are early pathological phenomena. This review concentrates on two of the most prevalent neurodegenerative diseases: Alzheimer’s disease (AD) and Parkinson’s disease (PD) and would be aimed to discuss the role of mitochondrial in pathogenesis of neurodegenerative diseases, providing new direction for further research.

Key words: mitochondrion, Alzheimer&, rsquo, s disease, Parkinson&, rsquo, s disease

中图分类号:

R741

周晓雯, 苏朝芬, 罗焕敏. 线粒体与神经退行性疾病[J]. 神经药理学报, 2011, 1(3): 41-46.

Zhou Xiao-wen, Su Chao-fen, Luo Huan-min. Mitochondria and Neurodegenerative Diseases[J]. ACTA NEUROPHARMACOLOGICA, 2011, 1(3): 41-46.

参考文献

1 Appel SH, Smith RG, Le WD. Immune-mediated cell death in neurodegenerative disease[J].Adv Neurol,1996, 69:153-159
2 John Hardy. Pathways to primary neurodegenerative disease[J]. Neurologia，2002,17(8):399-401
3 朱兴族.神经退行性疾病病变机理及药物作用新靶点.科技前沿与学术评论[J]，1999,21(6)：42-46
4 高欣，唐希灿.神经退行性疾病的早期信号：线粒体功能障碍[J].生命科学，2006，18(2)：138-143
5 张均田.脑缺血、葡萄糖/能量代谢障碍与神经退行性疾病[J]. 中国药理通讯, 2000(16):241-246
6 Minoshima S, iordani B, Berent S, et al. Metabolic reduction in the posterior cingulated cortex in very early Alzheimer's disease[J]. Ann Neurol, 1997(42):85-94
7 Ellen A A Nollen, Richard Morimoto. Chaperoning signaling pathways: molecular chaperones as stress-sensing ‘heat shock’ proteins[J].J Cell Sci,2002(115):2809-2816
8 辛颖.线粒体与神经退行性病变[J].医学综述，2008,14(4):520-521
9 Mahyar Etrninan，Sudeep S Gill，Ali Samii. Intake of vitamin E，vitamin C，and carotenoids and the risk of Parkinson’S disease：a metaanalysis[J]. Lancet Neurol, 2005(4):362-365
10 Edgar R. Miller, Pastor-Barriuso Pastor, Darshan Dalai, et al. Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality[J]. Ann Int Med, 2005(142):37-46
11 Enrique Cadenas, Kelvin J.A.Davies. Mitochondrial free radical generation, oxidative stress, and aging[J]. Free Radic BiolMed, 2000(29): 222-230
12 韩玲,陈可冀.氧应激对线粒体呼吸链的影响及益心康的作用[J]. 中国心血管病杂志,2002,7(2):115-117
13 刘新,邹典定,王大斌,明萌,刘志祥.海马神经元兴奋性毒性模型的建立及其意义[J]. Stroke and Nervous Diseases,2006,13(3):138-141
14 许康，张苏明.线粒体损伤与神经元缺血死亡[J].国外医学脑血管疾病分册，2002,10(6):461-464
15 Dae-Won Seo, Maria-Leonor Lopez-Meraz, Suni Allen, Claude Guy Wasterlain, Jerome Niquet. Contribution of a mitochondrial pathways to excitotoxic neuronal necrosis[J]. J Neurosci Res, 2009, 87(9): 2087–2094
16 Dong Xiaoxia, Wang Yan, Qin Zhenghong. Molecular mechanism s of excitotoxicity and their relevance to pathogenesis of rodegenerative diseases[J]. Acta Pharmacol Sin, 2009(4):379～387
17 唐小卿,赵静,杨春涛,申新田等.非对称性二甲基精氨酸保护PC12细胞拮抗谷氨酸兴奋性毒性的损伤作用[J].中国病理生理杂志,2009 ( 2): 248- 253
18 Michael T.Lin, M.Flint Beal. Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases[J]. Nature,2006,443 (7113): 787–795
19 Douglas R.Green, Guido Kroemer. The pathophysiology of mitochondrial cell death[J]. Science, 2004,305(5684): 626-629
20 Celine Cande, Francesco Cecooni, Philippe Dessen, et al. Apoptosis-inducing factor（AIF）：key to the caspase independent pathways of cell death[J]. J Cell Sci, 2002,115(24):4727-4734
21 Ryuji Hata , Keiichiro Maeda , Dirk Hermann, et al. Evolution of brain infarction after transient focal cerebral ischemia in mice[J]. J Cereb Blood Flow Metab,2000(20):937-946
22 李宜培.线粒体损伤与细胞凋亡[J].河南职工医学院学报，2008,20(1):94-97
23 刘志安，赵娓娓，吕春娥，李梅，徐铁军. AD样大鼠海马NMDAR亚单位2B和2A的表达及其与细胞凋亡的关系[J].山东大学学报，2011(2)：14-18.
24 刘新红，周广安. 原位杂交检测FADD和TH mRNA在PD模型大鼠黑质中的表达变化及与凋亡的关系[J].泰山医学院学报，2011(4):254-256.
25 P.Hemachandra Reddy. Amyloid beta, mitochondrial structural and functional dynamics in Alzheimer′s disease[J]. Exp Neurol, 2009, 218(2): 286-292
26 Gjumrakch Aliev, Eldar Gasimov, Mark E Obrenovic, et al. Atherosclerotic lesions and mitochondria DNA deletions in brain microvessels: implication in the pathogenesis of Alzheimer’s disease[J]. Vasc Health Risk Manag, 2008(4):721–730
27 Latha Devi , Hindupur K. Anandatheerthavarada . Mitochondrial trafficking of APP and alpha synuclein: relevance to mitochondrial dysfunction in Alzheimer’s and Parkinson’s diseases[J]. Biochim Biophys Acta, 2010( 1802):11–19
28 Querfurth HW, LaFerla FM. Alzheimer’s disease[J]. N Engl J Med, 2010 (362):329–344
29 Casley CS, Canevari L, Land JM, Clark JB, Sharpe MA. Beta-amyloid inhibits integrated mitochondrial respiration and key enzyme activities[J]. J Neurochem, 2002(80):91-100
30 Casley CS, Land JM, Sharpe MA, Clark JB, Duchen MR, Canevari L. Beta-amyloid fragment 25-35 causes mitochondrial dysfunction in primary cortical neurons[J]. Neurobiol Dis,2002(10):258-267
31 Casper Caspersen, Wang Ning, Yao Jun, et al. Mitochondrial Abeta: a potential focal point for neuronal metabolic dysfunction in Alzheimer’s disease[J]. FASEBJ,2005(19):2040–204
32 Virginie Rhein , Song Xiaomin, Andreas Wiesner, et al. Amyloid-beta and tau synergistically impair the oxidative phosphorylation system in triple transgenic Alzheimer’s disease mice[J]. Proc Natl Acad Sci USA , 2009,(106):20057–20062
33 Gunnar K Gouras, Claudia G Almeida, Reisuke Takahashi. Intraneuronal Abeta accumulation and origin of plaques in Alzheimer’s disease[J]. Neurobiol Aging, 2005(26):1235–1244
34 Peter J.Crouch, Rachel Blake, James A.Duce, et al. Copper-dependent inhibition of human cytochrome c oxidase by a dimeric conformer of amyloid-beta 1–42[J].J Neurosci,2005(25):672–679
35 Patricia A Trimmer, Paula M Keeney, M Kate Borland, et al. Mitochondrial abnormalities in cybrid cell models of sporadic Alzheimer’s disease worsen with passage in culture[J]. Neurobiol Dis, 2004(15):29–39
36 徐淑君，刘桂兰. β淀粉样蛋白导致的线粒体损伤研究进展[J].生物化学与生物物理进展，2010,37(6):589-593
37 Vanessa A Morais, De Strooper Bart. Mitochondria dysfunction and neurodegenerative disorders: Cause or Consequence[J]. J Alzheimers Dis, 2010(20): S255–S263
38 Choudhary S, Zhang W, Zhou F, et al. Cellular lipid peroxidation endroducts induce apoptosis in human lens epithelial cells[J].Free Radic Biol Med,2002(32):360 – 3691
39 David C Chan. Mitochondrial fusion and fission in mammals[J].Ann Rev Cell Dev Biol ,2006(22):79–99
40. Wang Xinglong, Su Bo, Hisashi Fujioka, Zhu Xiongwei. Dynamin-like protein 1 reduction underlies mitochondrial morphology and distribution abnormalities in fibroblasts from sporadic Alzheimer’s disease patients[J]. Am J Pathol, 2008(173):470–482
41 Wang Xinglong, Su Bo, Sandra L. Siedlak , et al. Amyloid-beta overproduction causes abnormal mitochondrial dynamics via differential modulation of mitochondrial fission/fusion proteins[J]. Proc Natl Acad Sci USA, 2008(105):19318–19323
42 Cho Dong-Hyung, Tomohiro Nakamura, Fang Jianguo, et al. S- nitrosylation of Drp1 mediates β－amyloid－related mitochondrial fission and neuronal injury[J]. Science,2009，324(5923): 102－105
43 Deng Hansong, Mark W Dodson, Huang Haixia, et al. The Parkinson’s disease genes pink1 and pakin promote mitochondrial fission and/or inhibit fusion in Drosophila[J]. Proc Natl Acad Sci U S A,2008,105( 38): 14503－14508
44 Zhang Juan, Liu Wweihua, Liu Jianchao,et al. G protein β2 subunit interacts with mitofusin 1 to regulate mitochondrial fusion[J]. Nature Communication, 2010(1):101-110

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