5- 脂氧合酶与阿尔茨海默病

doi:10.3969/j.issn.2095-1396.2016.05.006

神经药理学报 ›› 2016, Vol. 6 ›› Issue (5): 39-44.DOI: 10.3969/j.issn.2095-1396.2016.05.006

5- 脂氧合酶与阿尔茨海默病

杜贯涛，张春腾，洪浩

1. 南京医科大学附属常州市第二人民医院药学部，常州，213003，中国
2. 中国药科大学药学院药理教研室，南京，210009，中国

出版日期:2016-10-26 发布日期:2017-01-03
通讯作者: 洪浩，男，博士，教授，博士生导师；研究方向：神经精神药理；Tel：+86-025-86185227，E-mail：honghao@cpu.edu.cn
作者简介:杜贯涛，男，主管药师；研究方向：临床药学；Tel：+86-025-86185227，E-mail：cpudgt@sina.com
基金资助:
国家自然科学基金面上项目（No.81273497，NO.81573413）

Progress on Research of 5-Lipoxygenase in Alzheimer’s Disease

DU Guan-tao，ZHANG Chun-teng，HONG Hao

1. Department of Pharmacy，Nanjing Medical University Subsidiary Changzhou No.2 People’s Hospital，Changzhou，213003，China
2. Department of Pharmacology，China Pharmaceutical University，Nanjing，210009，China

Online:2016-10-26 Published:2017-01-03
Contact: 洪浩，男，博士，教授，博士生导师；研究方向：神经精神药理；Tel：+86-025-86185227，E-mail：honghao@cpu.edu.cn
About author:杜贯涛，男，主管药师；研究方向：临床药学；Tel：+86-025-86185227，E-mail：cpudgt@sina.com
Supported by:
国家自然科学基金面上项目（No.81273497，NO.81573413）

摘要/Abstract

摘要： 5- 脂氧合酶（5-lipoxygenase，5-LOX）是催化花生四烯酸（arachidonic acid，AA）生成5- 羟基-6，8，11，14- 二十碳四烯酸（5-hydroperoxy-6，8，11，14-eicosatetraenoic acid，5-HPETE）和各种白三烯（leukotrienes，LTs）类物质的关键酶。近年来研究显示，5-LOX 参与阿尔茨海默病（Alzheimer’s disease，AD）的病理生理过程。抑制5-LOX 可以降低β淀粉样蛋白（β-amyloid peptide，Aβ）的沉积、tau 蛋白磷酸化、减轻神经炎症反应和调节突触功能，改善AD 的认知功能障碍。该文就5-LOX 与AD 相关性研究进展进行综述。

关键词: 阿尔茨海默病, 5- 脂氧合酶, &, beta, 淀粉样蛋白, tau, 神经炎症, 突触

Abstract: 5-lipoxygenase plays a key role in catalyzing the conversion of arachidonic acid （AA） to 5-hydroperoxy-6，8，11，14-eicosatetraenoic acid （5-HPETE），which can then be metabolized into different leukotrienes （LTs）. The recently studies have shown that 5-lipoxygenase is involved in the pathophysiology of Alzheimer’s disease. Inhibition of 5-lipoxygenase decreases amyloid β peptide （Aβ） and tau hyperphosphorylation，mitigates neuroinflammation，regulates synaptic function and ameliorates cognitive disorders in Alzheimer’s disease. In this review，we will summarize studies of 5-lipoxygenase in Alzheimer’s disease pathogenesis.

Key words: Alzheimer&, rsquo, s disease, 5-lipoxygenase, &, beta, -amyloid peptide, tau, neuroinflammation

杜贯涛，张春腾，洪浩. 5- 脂氧合酶与阿尔茨海默病[J]. 神经药理学报, 2016, 6(5): 39-44.

DU Guan-tao，ZHANG Chun-teng，HONG Hao. Progress on Research of 5-Lipoxygenase in Alzheimer’s Disease[J]. Acta Neuropharmacologica, 2016, 6(5): 39-44.

参考文献

[1] Danubia Bonfanti Dos Santos, Dirleise Colle, Eduardo Luiz Gasnhar Moreira, et al. Probucol mitigates streptozotocin-induced cognitive and biochemical changes in mice [J]. Neuroscience, 2015, 284: 590-600.

[2] Thomas Wisniewski, Fernando Goñi. Immunotherapeutic approaches for Alzheimer’s disease [J]. Neuron, 2015, 85(6): 1162-1176.

[3] Yash B Joshi, Domenico Praticò. The 5-lipoxygenase pathway: oxidative and inflammatory contributions to the Alzheimer's disease phenotype [J]. Frontiers in Cellular Neuroscience, 2015, 8: 436.

[4] Phillip F Giannopoulos, Yash B Joshi, Domenico Praticò. Novel lipid signaling pathways in Alzheimer's disease pathogenesis [J]. Biochem Pharmacol, 2014, 88(4): 560-564.

[5] Omidreza Firuzi, Zhuo Jia-min, Cinzia M Chinnici, et al. 5-Lipoxygenase gene disruption reduces amyloid-β pathology in a mouse model of Alzheimer’s disease [J]. FASEB J, 2008, 22(4): 1169-1178.

[6] Milos D Ikonomovic, Eric E Abrahamson, Tolga Uz, et al. Increased 5-lipoxygenase immunoreactivity in the hippocampus of patients with Alzheimer's disease [J]. J Histochem Cytochem, 2008, 56(12): 1065-1073.

[7] Elvira Valera, Richard Dargusch, Pamela A Maher, et al. Modulation of 5-lipoxygenase in proteotoxicity and Alzheimer's disease [J]. J Neuroscience the Official J Society for Neuroscience, 2013, 33(22):10512-10525.

[8] Chu Jin, Phillip F Giannopoulos, Carolina Ceballos-Diaz, et al. 5-Lipoxygenase gene transfer worsens memory, amyloid, and tau brain pathologies in a mouse model of alzheimer disease [J]. Ann Neurol, 2012, 72(3): 442-454.

[9] Olof P Rådmark. The molecular biology and regulation of 5-lipoxygenase [J]. Am J Respir Crit Care Med, 2000, 161(1): S11-15.

[10] Chu Jin, Domenico Praticò. The 5-lipoxygenase as a common pathway for pathological brain and vascular aging [J]. Cardiovasc Psychiatry Neurol, 2009, 2009: 174657. doi: 10.1155/2009/174657.

[11] Kausik Bishayee, Anisur Rahman Khudabukhsh. 5-lipoxygenase antagonist therapy: a new approach towards targeted cancer chemotherapy [J]. Acta Biochimica Et Biophysica Sinica, 2013, 45(9): 709-719.

[12] Rakesh Kumar Singh, Suman Gupta, Sunanda Dastidar, et al. Cysteinyl leukotrienes and their receptors: molecular and functional characteristics [J]. Pharmacology, 2010, 85(6): 336-349.

[13] Takehiko Yokomizo, Takashi Izumi, Takao Shimizu. Leukotriene B4: metabolism and signal transduction [J]. Arch Biochem Biophys, 2001, 385(2): 231-241.

[14] Tang Su-su, Wang Xiao-yun, Hong Hao, et al. Leukotriene D4 induces cognitive impairment through enhancement of CysLT1R-mediated amyloid-β generation in mice [J]. Neuropharmacology, 2013, 65: 182-192.

[15] Milos D Ikonomovic, Eric E Abrahamson, Tolga Uz, et al. Increased 5-lipoxygenase immunoreactivity in the hippocampus of patients with Alzheimer's disease [J]. J Histochem Cytochem, 2008, 56(12): 1065-1073.与6重复

[16] Elvira Valera, Richard Dargusch, Pamela A Maher, et al. Modulation of 5-lipoxygenase in proteotoxicity and Alzheimer's disease [J]. J Neurosci, 2013, 33(25): 10512-10525.与7重复

[17] Cinzia M Chinnici, Yao Yue-mang, Domenico Praticò. The 5-lipoxygenase enzymatic pathway in the mouse brain: young versus old [J]. Neurobiol Aging, 2007, 28(9): 1457-1462.

[18] Omidreza Firuzi, Zhuo Jia-min, Cinzia M Chinnici, et al. 5-Lipoxygenase gene disruption reduces amyloid-beta pathology in a mouse model of Alzheimer's disease [J]. FASEB J, 22(4): 1169-1178.

[19] Florinda Listì, Calogero Caruso, Domenico Lio, et al. Role of cyclooxygenase-2 and 5-lipoxygenase polymorphisms in Alzheimer's disease in a population from northern Italy: implication for pharmacogenomics [J]. J Alzheimers Disease Jad, 2010, 19(2): 551-557.

[20] Phillip F Giannopoulos, Yash B Joshi, Domenico Praticò. Novel lipid signaling pathways in Alzheimer's disease pathogenesis [J]. Biochem Pharmacol, 2014, 88(4): 560-564.与4重复

[21] Chu Jin, Domenico Praticò. 5-lipoxygenase as an endogenous modulator of amyloid β formation in vivo [J]. Ann Neurol, 2011, 69(1): 34–46.

[22] Chu Jin, Domenico Praticò. Pharmacologic blockade of 5-lipoxygenase improves the amyloidotic phenotype of an Alzheimer's disease transgenic mouse model involvement of γ-secretase [J]. Am J Pathol, 2011, 178(4): 1762-1769.

[23] Chu Jin, Li Jin-guo, Domenico Praticò. Zileuton improves memory deficits, amyloid and tau pathology in a mouse model of Alzheimer's disease with plaques and tangles [J]. PLoS One, 2013, 8(8): e70991.

[24] Chu Jin, Domenico Praticò. The 5-Lipoxygenase as modulator of Alzheimer's γ-secretase and therapeutic target [J]. Brain Res Bull, 2016, 126(Pt 2): 207-212.

[25] Chu Jin, Li Jian-guo, Nicholas E Hoffman, et al. Regulation of gamma-secretase activating protein by the 5Lipoxygenase: in vitro and in vivo evidence [J]. Scientific Reports, 2015, 5:11086.

[26] Chu Jin, Li Jian-guo, Yash B Joshi, et al. Gamma secretase-activating protein is a substrate for caspase-3: implications for Alzheimer’s disease [J]. Biol Psychiatry, 2015, 77(8):720-728.

[27] Ren Qing-guo, Liao Xiao-mei, Chen Xiao-qian, et al. Effects of tau phosphorylation on proteasome activity [J]. FEBS Lett, 2007, 581(7): 1521-1528.

[28] Liu Gong-ping, Wei Wei, Zhou Xin, et al. I(2)(PP2A) regulates p53 and Akt correlatively and leads the neurons to abort apoptosis [J]. Neurobiol Aging, 2012, 33(2): 254-264.

[29] Chu Jin, Li Jian-guo, Carolina Ceballos-Diaz, et al. The influence of 5-lipoxygenase on Alzheimer's disease-related tau pathology: in vivo and in vitro evidence [J]. Biol Psychiatry, 2013, 74(5): 321-328.

[30] Antonio Di Meco, Elisabetta Lauretti, Alana N Vagnozzi, et al. Zileuton restores memory impairments and reverses amyloid and tau pathology in aged AD mice [J]. Neurobiol Aging, 2014, 35(11): 2458-2464.

[31] Helmut Kettenmann, Frank Kirchhoff, Alexei Verkhratsky. Microglia: new roles for the synaptic stripper [J]. Neuron, 2013, 77(1):10-18.

[32] Uwe-Karsten Hanisch, Helmut Kettenmann. Microglia: active sensor and versatile effector cells in the normal and pathologic brain [J]. Nat Neurosci, 2007, 10(11): 1387-1394.

[33] Helmut Kettenmann, Uwe-Karsten Hanisch, Mami Noda M, et al. Physiology of microglia[J]. Physiol Rev, 2011, 91(2): 461-553.

[34] Patrick L Mcgeer, Edith G M Mcgeer. Targeting microglia for the treatment of Alzheimer’s disease [J]. Glia, 2015, 19(4): 497-506.

[35] Olof Rådmark, Bengt Samuelsson. Regulation of the activity of 5-lipoxygenase, a key enzyme in leukotriene biosynthesis [J]. Biochem Biophys Res Commun, 2010, 396(1): 105-110.

[36] Yash B Joshi, Phillip F Giannopoulos, Chu Jin, et al. Modulation of lipopolysaccharide-induced memory insult, γ-secretase, and neuroinflammation in triple transgenic mice by 5-lipoxygenase [J]. Neurobiol Aging, 2014, 35(5): 1024-1031.

[37] Jin Chu, Domenico Praticò. Involvement of 5-lipoxygenase activating protein in the amyloidotic phenotype of an Alzheimer’s disease mouse model [J]. J Neuroinflammation, 2012, 9: 127.

[38] Ashok Kumar, Sorabh Sharma, Ashwani Prashar, et al. Effect of licofelone--a dual COX/5-LOX inhibitor in intracerebroventricular streptozotocin-induced behavioral and biochemical abnormalities in rats [J]. J Mol Neurosci, 2015, 55(3): 749-759.

[39] Murtishaw A S, Heaney C F, Bolton M M, et al. Effect of acute lipopolysaccharide-induced inflammation in intracerebroventricular-streptozotocin injected rats [J]. Neuropharmacology, 2015, 101: 110-122.

[40] Pradip K Kamat, Anuradha Kalani, Shivika Rai, et al. Streptozotocin intracerebroventricular-induced neurotoxicity and brain insulin resistance: a therapeutic intervention for treatment of sporadic Alzheimer's disease (sAD)-like pathology [J]. Mol Neurobiol, 2016, 53(7): 4548-4562.

[41] Lai Jine, Hu Meng, Wang Hao, et al. Montelukast targeting the cysteinyl leukotriene receptor 1 ameliorates Aβ1-42-induced memory impairment and neuroinflammatory and apoptotic responses in mice [J]. Neuropharmacology, 2014, 79: 707-714.

[42] Zhang Chun-teng, Lin Jing-ran, Wu Feng, et al. Montelukast ameliorates streptozotocin-induced cognitive impairment and neurotoxicity in mice [J]. Neurotoxicology, 2016, 57: 214-222.

[43] Julia Marschallinger, Iris Schäffner, Barbara Klein, et al. Structural and functional rejuvenation of the aged brain by an approved anti-asthmatic drug [J]. Nature Communications, 2015, 6: 8466.

[44] Chu Jin, Phillip F Giannopoulos, Carolina Ceballos-Diaz, et al. Adeno-associated virus-mediated brain delivery of 5-lipoxygenase modulates the AD-like phenotype of APP mice [J]. Molecular Neurodegeneration, 2012, 7(1): 1.

[45] Chu J, Giannopoulos PF, Ceballos-Diaz C, et al. 5-Lipoxygenase gene transfer worsens memory, amyloid, and tau brain pathologies in a mouse model of alzheimer disease [J]. Ann Neurol, 2012, 72(3): 442-454.与8重复

[46] Phillip Fotios Giannopoulos, Chu Jin, Yash B Joshi, et al. Gene knockout of 5-lipoxygenase rescues synaptic dysfunction and improves memory in the triple-transgenic model of Alzheimer’s disease [J]. Mol Psychiatry, 2013, 19(4): 511-518.

5- 脂氧合酶与阿尔茨海默病

Progress on Research of 5-Lipoxygenase in Alzheimer’s Disease

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

[1]	谢彬, 黄志源, 林多朵, 杨福龙, 谢奕彬. 针药结合干预阿尔茨海默病抑郁症状效果分析[J]. 神经药理学报, 2020, 10(5): 5-8.
[2]	赵雨薇, 甄艳杰, 戴月英, 沈丽霞. 槲皮素对阿尔茨海默症神经保护作用研究[J]. 神经药理学报, 2020, 10(5): 55-64.
[3]	刘畅, 孟宪勇, 董晓华. 阿尔茨海默症的发病机制及治疗药物研究进展[J]. 神经药理学报, 2020, 10(4): 36-40.
[4]	海吉涛, 罗焕敏. 病原微生物与阿尔茨海默病相关性研究进展[J]. 神经药理学报, 2020, 10(4): 58-64.
[5]	杨旭华, 杜爽, 沈丽霞, 郝军荣. 阿尔茨海默病的药物治疗研究进展[J]. 神经药理学报, 2020, 10(3): 47-53.
[6]	甄艳杰, 郭童林, 赵雨薇, 沈丽霞. 植物雌激素介导线粒体途径对阿尔茨海默病神经保护作用的研究进展[J]. 神经药理学报, 2020, 10(1): 40-46.
[7]	杨琳，艾静. 脑源雌激素在阿尔茨海默病中的作用研究进展[J]. 神经药理学报, 2019, 9(5): 50-64.
[8]	张帅，艾静. 谷氨酸功能异常与阿尔茨海默病[J]. 神经药理学报, 2018, 8(6): 9-20.
[9]	LIU Cai-hong，WU Xian，TANG Su-su，HONG Hao. Involvement of TGR5 in Aβ-Induced Neurotoxicity in Vivo*[J]. 神经药理学报, 2018, 8(4): 11-12.
[10]	SHEN li-xia1，LIU Liang-liang1，ZHANG Ming1，LIU Yang1，ZHANG Dan-shen 2. Research of Quercetin’s Estrogen-Like Action on Central Nervous System and Its Mechanisms*[J]. 神经药理学报, 2018, 8(4): 23-25.
[11]	WU Xian, LV Yang-ge, TANG Su-Su, HONG Hao. Involvement of TGR5 in Aβ-induced Neurotoxicity in Vivo[J]. 神经药理学报, 2018, 8(4): 53-54.
[12]	孙毅，谭博，苏瑞斌. 偏向性配体——阿片类镇痛药设计新思路[J]. 神经药理学报, 2018, 8(2): 1-7.
[13]	王晋辉，黄丽，陈娜. 大脑皮层GABA 能神经元缺血性损伤：易损性，机制和病理影响[J]. 神经药理学报, 2018, 8(2): 8-25.
[14]	CHEN Fang，Arijit Ghosh，TANG Su-su，HONG Hao. Preventive Effect of Genetic Knockdown and Pharmacological Blockade of CysLT1R on Lipopolysaccharide（LPS）-induced Memory Deficit and Neurotoxicity in vivo[J]. 神经药理学报, 2018, 8(2): 29-29.
[15]	黄蕊，杨翠翠，张兰. 二苯乙烯苷对APP/PS1 双转基因小鼠学习记忆及突触可塑性的影响[J]. 神经药理学报, 2018, 8(2): 31-31.