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化学进展 2018, Vol. 30 Issue (10): 1592-1600 DOI: 10.7536/PC180609 前一篇   

• 综述 •

帕金森病中的关键金属元素

黄辉1,2, 陈俊1,2, 卢会茹1, 周梦雪1,2, 胡毅1,2*, 柴之芳1,2,3   

  1. 1. 中国科学院高能物理研究所 北京 100049;
    2. 中国科学院大学 北京 100049;
    3. 苏州大学放射医学及交叉学科研究院/江苏高校放射医学协同创新中心 苏州 215123
  • 收稿日期:2018-06-06 修回日期:2018-06-24 出版日期:2018-10-15 发布日期:2018-09-25
  • 通讯作者: 胡毅 E-mail:huyi@ihep.ac.cn
  • 基金资助:
    国家自然科学基金项目（No.11375213，21390411）资助
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Neurotoxicity of Key Metals in Parkinson's Disease

Hui Huang1,2, Jun Chen1,2, Huiru Lu1, Mengxue Zhou1,2, Yi Hu1,2*, Zhifang Chai1,2,3   

  1. 1. Institute of High Energy Physics, Chinese Academy of Sciences, Beijing 100049, China;
    2. University of Chinese Academy of Sciences, Beijing 100049, China;
    3. School for Radiological and Interdisciplinary Sciences(RAD-X) and Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou 215123, China
  • Received:2018-06-06 Revised:2018-06-24 Online:2018-10-15 Published:2018-09-25
  • Supported by:
    The work was supported by the National Natural Science Foundation of China(No. 11375213, 21390411).
随着我国人口日趋老龄化，老年退行性疾病呈高发态势，据估计当今我国帕金森病患者占世界一半左右。因此，帕金森病日益成为危害我国人民生命健康的突出问题之一。当前临床上对帕金森病无有效治愈手段，而且对于帕金森病的发病机制仍无定论。在诸多可能的诱因中，过渡金属元素的内稳态失衡和氧化应激，被认为与帕金森病相关。本文以生物体两种必需的过渡金属元素铁和铜为中心，介绍了与细胞内铁元素和铜元素代谢相关的信号通路和基因蛋白，并阐述了铁元素或铜元素稳态失衡对神经细胞造成损伤的可能机制。最后，介绍了同步辐射技术应用于帕金森病中元素分析和机制的研究进展，并展望了帕金森病中生物无机问题的未来研究方向。
关键词： 帕金森病, 铁, 铜, 氧化应激, 同步辐射
As China's aging population continues to increase, it is estimated that people with Parkinson's disease (PD) in China account for about half of PD cases in the world. Therefore, PD has become one of the fastest growing threats to public health in China. Currently, there is no cure for PD. The etiology and pathogenesis of PD remain elusive. Metal dyshomeostasis and oxidative stress are deemed as important risk factors for PD. Herein, recent advances in the neurotoxicity of key metals in PD are reviewed, and possible mechanisms underlying iron/copper-mediated neuron lesion are discussed. In addition, the application of synchrotron radiation in elemental analysis and mechanistic study of PD are briefly introduced. Lastly, the challenges and perspectives for bioinorganic chemistry in PD are discussed.
Contents
1 Introduction
2 The issues of bioinorganic chemistry in Parkinson's disease
2.1 Oxidative stress
2.2 Metal homeostasis
3 Iron in Parkinson's disease
3.1 Ferroptosis
3.2 Interaction between iron cations and proteins
3.3 Iron chelators
4 Copper in Parkinson's disease
4.1 Copper homeostasis
4.2 Interaction between cupric ions and α-synuclein
5 The application of synchrotron radiation-based elemental analysis to Parkinson's disease
6 Conclusion and outlook
Key words: Parkinson's disease, iron, copper, oxidative stress, synchrotron radiation

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[1] Burbulla L F, Song P, Mazzulli J R, Zampese E, Wong Y C, Jeon S, Santos D P, Blanz J, Obermaier C D, Strojny C, Savas J N, Kiskinis E, Zhuang X, Kruger R, Surmeier D J, Krainc D. Science, 2017, 357:1255.
[2] Mittal S, Bjornevik K, Im D S, Flierl A, Dong X, Locascio J J, Abo K M, Long E, Jin M, Xu B, Xiang Y K, Rochet J C, Engeland A, Rizzu P, Heutink P, Bartels T, Selkoe D J, Caldarone B J, Glicksman M A, Khurana V, Schule B, Park D S, Riise T, Scherzer C R. Science, 2017, 357:891.
[3] Hu Y, Tong Y R. Sci. Signal., 2010, 3:pe13.
[4] 刘疏影(Liu S Y), 陈彪(Chan P). 中国现代神经疾病杂志(Chinese Journal of Contemporary Neurology and Neurosurgery), 2016, 16:98.
[5] Ascherio A, Schwarzschild M A. Lancet Neurol., 2016, 15:1257.
[6] Lan A P, Chen J, Chai Z F, Hu Y. Biometals, 2016, 29:665.
[7] Liu Y, Li H P, Xie J, Zhou M X, Huang H, Lu H R, Chai Z F, Chen J, Hu Y. Biomater. Sci., 2017, 5:1022.
[8] Guzman J N, Sanchez-Padilla J, Wokosin D, Kondapalli J, Ilijic E, Schumacker P T, Surmeier D J. Nature, 2010, 468:696.
[9] Li Y, Ren M, Wang X Q, Cui X X, Zhao H M, Zhao C R, Zhou J, Guo Y A, Hu Y, Yan C, Berk B, Wang J. Sci. Rep., 2017, 7:15539.
[10] Herculano-Houzel S. Plos One, 2011, 6:e17514.
[11] Zhou Q, Liu C, Liu W, Zhang H, Zhang R, Liu J, Zhang J, Xu C, Liu L, Huang S, Chen L. Toxicol. Sci., 2015, 143:81.
[12] Ojha S, Javed H, Azimullah S, Abul Khair S B, Haque M E. Neurotox. Res., 2016, 29:275.
[13] Medeiros M S, Schumacher-Schuh A, Cardoso A M, Bochi G V, Baldissarelli J, Kegler A, Santana D, Chaves C M, Schetinger M R, Moresco R N, Rieder C R, Fighera M R. PLoS One, 2016, 11:e0146129.
[14] Giordano S, Darley-Usmar V, Zhang J. Redox Biol., 2014, 2:82.
[15] Tan Y, Liu R C, Zhang H T, Peltier R, Lam Y W, Zhu Q, Hu Y, Sun H Y. Sci. Rep., 2015, 5:16979.
[16] Choi Y B, Tenneti L, Le D A, Ortiz J, Bai G, Chen H S, Lipton S A. Nat. Neurosci., 2000, 3:15.
[17] Sen N, Hara M R, Ahmad A S, Cascio M B, Kamiya A, Ehmsen J T, Agrawal N, Hester L, Dore S, Snyder S H, Sawa A. Neuron, 2009, 63:81.
[18] Akhtar M W, Sunico C R, Nakamura T, Lipton S A. Int. J. Cell Biol., 2012, 2012:463756.
[19] Bashkatova V, Alam M, Vanin A, Schmidt W J. Exp. Neurol., 2004, 186:235.
[20] Uehara T, Nakamura T, Yao D, Shi Z Q, Gu Z, Ma Y, Masliah E, Nomura Y, Lipton S A. Nature, 2006, 441:513.
[21] Chen Z, Chen S J. Cell, 2017, 168:556.
[22] Lu C H, Lin Y F, Lin J J, Yu C S. PLoS One, 2012, 7:e39252.
[23] Hu Y, Wang G, Chen G Y, Fu X, Yao S Q. Electrophoresis, 2003, 24:1458.
[24] Lu H R, Li S H, Chen J, Xia J, Zhang J C, Huang Y, Liu X X, Wu H C, Zhao Y L, Chai Z F, Hu Y. Metallomics, 2015, 7:1508.
[25] Perl D P, Olanow C W. J. Neuropathol. Exp. Neurol., 2007, 66:675.
[26] Cersosimo M G, Koller W C. Neurotoxicology, 2006, 27:340.
[27] Dixon S J, Lemberg K M, Lamprecht M R, Skouta R, Zaitsev E M, Gleason C E, Patel D N, Bauer A J, Cantley A M, Yang W S, Morrison B, 3rd, Stockwell B R. Cell, 2012, 149:1060.
[28] Angeli J P F, Shah R, Pratt D A, Conrad M. Trends Pharmacol. Sci., 2017, 38:489.
[29] Massie A, Schallier A, Kim S W, Fernando R, Kobayashi S, Beck H, De Bundel D, Vermoesen K, Bannai S, Smolders I, Conrad M, Plesnila N, Sato H, Michotte Y. FASEB J., 2011, 25:1359.
[30] Gao M, Monian P, Quadri N, Ramasamy R, Jiang X. Mol. Cell, 2015, 59:298.
[31] Yang W S, Kim K J, Gaschler M M, Patel M, Shchepinov M S, Stockwell B R. Proc. Natl. Acad. Sci. U. S. A., 2016, 113:E4966.
[32] Doll S, Proneth B, Tyurina Y Y, Panzilius E, Kobayashi S, Ingold I, Irmler M, Beckers J, Aichler M, Walch A, Prokisch H, Trumbach D, Mao G, Qu F, Bayir H, Fullekrug J, Scheel C H, Wurst W, Schick J A, Kagan V E, Angeli J P, Conrad M. Nat. Chem. Biol., 2017, 13:91.
[33] Yang W S, Stockwell B R. Chem. Biol., 2008, 15:234.
[34] Hou W, Xie Y, Song X, Sun X, Lotze M T, Zeh H J, Kang R, Tang D. Autophagy, 2016, 12:1425.
[35] Mancias J D, Wang X, Gygi S P, Harper J W, Kimmelman A C. Nature, 2014, 509:105.
[36] Torii S, Shintoku R, Kubota C, Yaegashi M, Torii R, Sasaki M, Suzuki T, Mori M, Yoshimoto Y, Takeuchi T, Yamada K. Biochem. J., 2016, 473:769.
[37] Ayton S, Lei P. Biomed. Res. Int., 2014, 2014:581256.
[38] Belaidi A A, Bush A I. J. Neurochem., 2016, 139:179.
[39] Buijs M, Doan N T, van Rooden S, Versluis M J, van Lew B, Milles J, van der Grond J, van Buchem M A. Neurobiol. Aging, 2017, 53:20.
[40] Rhodes S L, Buchanan D D, Ahmed I, Taylor K D, Loriot M A, Sinsheimer J S, Bronstein J M, Elbaz A, Mellick G D, Rotter J I, Ritz B. Neurobiol. Dis., 2014, 62:172.
[41] Jiang H, Wang J, Rogers J, Xie J. Mol. Neurobiol., 2017, 54:3078.
[42] Ayton S, Lei P, Duce J A, Wong B X, Sedjahtera A, Adlard P A, Bush A I, Finkelstein D I. Ann. Neurol., 2013, 73:554.
[43] Hochstrasser H, Bauer P, Walter U, Behnke S, Spiegel J, Csoti I, Zeiler B, Bornemann A, Pahnke J, Becker G, Riess O, Berg D. Neurology, 2004, 63:1912.
[44] Hochstrasser H, Tomiuk J, Walter U, Behnke S, Spiegel J, Kruger R, Becker G, Riess O, Berg D. FASEB J., 2005, 19:1851.
[45] Kotzbauer P T, Truax A C, Trojanowski J Q, Lee V M. J. Neurosci., 2005, 25:689.
[46] Kubota A, Hida A, Ichikawa Y, Momose Y, Goto J, Igeta Y, Hashida H, Yoshida K, Ikeda S, Kanazawa I, Tsuji S. Mov. Disord., 2009, 24:441.
[47] Huang H, Chen J, Lu H R, Zhou M X, Chai Z F, Hu Y. Biometals, 2017, 30:623.
[48] Huang H, Chen J, Lu H R, Zhou M X, Chai Z F, Hu Y. Biometals, 2017, 30:975.
[49] Lan A P, Chen J, Zhao Y L, Chai Z F, Hu Y. Neuromol. Med., 2017, 19:1.
[50] Lu H R, Chen J, Huang H, Zhou M X, Zhu Q, Yao S Q, Chai Z F, Hu Y. Biometals, 2017, 30:599.
[51] Li X F, Zhang H T, Xie Y S, Hu Y, Sun H Y, Zhu Q. Org. Biomol. Chem., 2014, 12:2033.
[52] Peng Y, Wang C, Xu H H, Liu Y N, Zhou F. J. Inorg. Biochem., 2010, 104:365.
[53] He Q, Song N, Jia F, Xu H, Yu X, Xie J, Jiang H. Int. J. Biochem. Cell Biol., 2013, 45:1019.
[54] Febbraro F, Giorgi M, Caldarola S, Loreni F, Romero-Ramos M. Neuroreport, 2012, 23:576.
[55] Kaur D, Yantiri F, Rajagopalan S, Kumar J, Mo J Q, Boonplueang R, Viswanath V, Jacobs R, Yang L, Beal M F, DiMonte D, Volitaskis I, Ellerby L, Cherny R A, Bush A I, Andersen J K. Neuron, 2003, 37:899.
[56] Do Van B, Gouel F, Jonneaux A, Timmerman K, Gele P, Petrault M, Bastide M, Laloux C, Moreau C, Bordet R, Devos D, Devedjian J C. Neurobiol. Dis., 2016, 94:169.
[57] Devos D, Moreau C, Devedjian J C, Kluza J, Petrault M, Laloux C, Jonneaux A, Ryckewaert G, Garcon G, Rouaix N, Duhamel A, Jissendi P, Dujardin K, Auger F, Ravasi L, Hopes L, Grolez G, Firdaus W, Sablonniere B, Strubi-Vuillaume I, Zahr N, Destee A, Corvol J C, Poltl D, Leist M, Rose C, Defebvre L, Marchetti P, Cabantchik Z I, Bordet R. Antioxid. Redox Signal., 2014, 21:195.
[58] Lu H R, Zhang H T, Chen J, Zhang J C, Liu R C, Sun H Y, Zhao Y L, Chai Z F, Hu Y. Talanta, 2016, 146:477.
[59] Larner F, Sampson B, Rehkamper M, Weiss D J, Dainty J R, O'Riordan S, Panetta T, Bain P G. Metallomics, 2013, 5:125.
[60] Asthana A, Bollapalli M, Tangirala R, Bakthisaran R, Mohan Rao C. Free Radic. Biol. Med., 2014, 72:176.
[61] Huang H C, Hong L, Chang P, Zhang J, Lu S Y, Zheng B W, Jiang Z F. Neurotox. Res., 2015, 27:411.
[62] Zeeshan M, Murugadas A, Ghaskadbi S, Rajendran R B, Akbarsha M A. Comp. Biochem. Physiol. C Toxicol. Pharmacol., 2016, 185/186:1.
[63] Lan A P, Xiong X J, Chen J, Wang X, Chai Z F, Hu Y. Neurotox. Res., 2016, 30:499.
[64] Kobayashi H, Fukuhara K, Tada-Oikawa S, Yada Y, Hiraku Y, Murata M, Oikawa S. J. Neurochem., 2009, 108:397.
[65] Kumar V, Kalita J, Bora H K, Misra U K. Toxicol. Appl. Pharmacol., 2016, 293:37.
[66] Uriu-Adams J Y, Scherr R E, Lanoue L, Keen C L. BioFactors, 2010, 36:136.
[67] Valensin D, Dell'Acqua S, Kozlowski H, Casella L. J. Inorg. Biochem., 2016, 163:292.
[68] Mason R J, Paskins A R, Dalton C F, Smith D P. Biochemistry, 2016, 55:4737.
[69] Anandhan A, Rodriguez-Rocha H, Bohovych I, Griggs A M, Zavala-Flores L, Reyes-Reyes E M, Seravalli J, Stanciu L A, Lee J, Rochet J C, Khalimonchuk O, Franco R. Neurobiol. Dis., 2015, 81:76.
[70] Wang H, Wang M, Wang B, Li M, Chen H, Yu X, Zhao Y, Feng W, Chai Z. Metallomics, 2012, 4:289.
[71] Wang H, Wang M, Wang B, Li M, Chen H, Yu X, Yang K, Chai Z, Zhao Y, Feng W. Metallomics, 2012, 4:1113.
[72] You L H, Li F, Wang L, Zhao S E, Wang S M, Zhang L L, Zhang L H, Duan X L, Yu P, Chang Y Z. Neuroscience, 2015, 284:234.
[73] Walker T, Michaelides C, Ekonomou A, Geraki K, Parkes H G, Suessmilch M, Herlihy A H, Crum W R, So P W. Aging-US, 2016, 8:2488.
[74] Ortega R, Carmona A, Roudeau S, Perrin L, Ducic T, Carboni E, Bohic S, Cloetens P, Lingor P. Mol. Neurobiol., 2016, 53:1925.
[75] Colvin R A, Lai B, Holmes W R, Lee D. Metallomics, 2015, 7:1111.
[76] Surowka A D, Wrobel P, Adamek D, Radwanska E, Szczerbowska-Boruchowska M. Metallomics, 2015, 7:1522.
[77] Davies K M, Bohic S, Carmona A, Ortega R, Cottam V, Hare D J, Finberg J P, Reyes S, Halliday G M, Mercer J F, Double K L. Neurobiol. Aging, 2014, 35:858.
[78] Davies K M, Hare D J, Bohic S, James S A, Billings J L, Finkelstein D I, Doble P A, Double K L. Anal. Chem., 2015, 87:6639.
[79] Surowka A D, Topperwien M, Bernhardt M, Nicolas J D, Osterhoff M, Salditt T, Adamek D, Szczerbowska-Boruchowska M. Talanta, 2016, 161:368.
[80] Surowka A D, Wrobel P, Marzec M M, Adamek D, Szczerbowska-Boruchowska M. Spectroc. Acta Pt. B-Atom. Spectr., 2016, 123:47.
[81] Gao Y X, Peng X M, Zhang J C, Zhao J T, Li Y Y, Li Y F, Li B, Hu Y, Chai Z F. Metallomics, 2013, 5:913.
[82] Kumar A, Tamjar J, Waddell A D, Woodroof H I, Raimi O G, Shaw A M, Peggie M, Muqit M M, van Aalten D M. eLife, 2017, 6:e29985.
[83] Rodriguez J A, Ivanova M I, Sawaya M R, Cascio D, Reyes F E, Shi D, Sangwan S, Guenther E L, Johnson L M, Zhang M, Jiang L, Arbing M A, Nannenga B L, Hattne J, Whitelegge J, Brewster A S, Messerschmidt M, Boutet S, Sauter N K, Gonen T, Eisenberg D S. Nature, 2015, 525:486.
[84] Hahl H, Moller I, Kiesel I, Campioni S, Riek R, Verdes D, Seeger S. ACS Chem. Neurosci., 2015, 6:374.
[85] Araki K, Yagi N, Ikemoto Y, Yagi H, Choong C J, Hayakawa H, Beck G, Sumi H, Fujimura H, Moriwaki T, Nagai Y, Goto Y, Mochizuki H. Sci. Rep., 2015, 5:17625.
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摘要

帕金森病中的关键金属元素