药学学报, 2014, 49(10): 1372-1376
引用本文:
耿海局, 罗焕敏. 金属与阿尔茨海默病的研究进展[J]. 药学学报, 2014, 49(10): 1372-1376.
GENG Gelite, LUO Huan-min. The research progress of metals correlated to Alzheimer’s disease[J]. Acta Pharmaceutica Sinica, 2014, 49(10): 1372-1376.

金属与阿尔茨海默病的研究进展
耿海局1, 罗焕敏1,2
1. 暨南大学医学院, 广东 广州 510632;
2. 暨南大学脑科学研究所, 广东 广州 510632
摘要:
阿尔茨海默病(Alzheimer's disease,AD)为一种神经退行性疾病,是导致成年人痴呆最常见的原因之一。人们对于该病的研究虽历时数百余年,其中Aβ学说、tau学说在AD中的作用得到广泛认可,但是有关AD的具体发病机制仍不十分清楚。可以明确的是,AD是一种多因素引起的疾病,除了遗传、衰老和生活习惯外,环境因素也不容忽视,一些金属元素,如铜、铝、锌和铁等都可能与AD密切相关。本文就这些金属元素与AD的相关研究进行简要概述。
关键词:    阿尔茨海默病                             
The research progress of metals correlated to Alzheimer’s disease
GENG Gelite1, LUO Huan-min1,2
1. School of Medicine, Jinan University, Guangzhou 510632, China;
2. Institution for Brain Science, Jinan University, Guangzhou 510632, China
Abstract:
Alzheimer's disease (AD) is a kind of neurodegenerative diseases, the most common cause of dementia. Although AD has been studied more than 100 years and the Aβ and tau theory are most widely accepted among the theories achieved, yet it is not really clear what the mechanism related to AD works up to now. However, it is certain that AD is a kind of diseases resulting from multi-causes. Except for causes correlated with heredity, aging and life habits, environmental role is worth taking into consideration as well. Some metals, such as copper, aluminum, zinc and iron et al, can also have close relationship with AD. Now, we make an overview on the correlative researches in the field.
Key words:    Alzheimer’s disease    copper    aluminum    zinc    iron   
收稿日期: 2014-05-04
基金项目: 国家自然科学基金资助项目(81173037);国家973项目(2011CB707500);广东省科技计划项目(2012B050300018)
通讯作者: 罗焕敏,Tel/Fax:86-20-85228869,E-mail:tlhm@jnu.edu.cn
Email: tlhm@jnu.edu.cn
相关功能
PDF(271KB) Free
打印本文
0
作者相关文章
耿海局  在本刊中的所有文章
罗焕敏  在本刊中的所有文章

参考文献:
[1] Tsai LH, Madabhushi R. Alzheimer's disease: a protective factor for the ageing brain [J]. Nature, 2014, 507: 439-440.
[2] Prince M, Bryce R, Albanese E, et al. The global prevalence of dementia: a systematic review and metaanalysis [J]. Alzheimers Dement, 2013, 9: 63-75.
[3] Nuttall JR, Oteiza PI. Zinc and the aging brain [J]. Genes Nutr, 2014, 9: 379.
[4] Faller P, Hureau C. Bioinorganic chemistry of copper and zinc ions coordinated to amyloid-beta peptide [J]. Dalton Trans, 2009, (7): 1080-1094.
[5] Hung YH, Bush AI, Cherny RA. Copper in the brain and Alzheimer's disease [J]. J Biol Inorg Chem, 2010, 15: 61-76.
[6] Himes RA, Park GY, Siluvai GS, et al. Structural studies of copper (I) complexes of amyloid-beta peptide fragments: formation of two-coordinate bis(histidine) complexes [J]. Angew Chem Int Ed Engl, 2008, 47: 9084-9087.
[7] Lutsenko S, Bhattacharjee A, Hubbard AL. Copper handling machinery of the brain [J]. Metallomics, 2010, 2: 596-608.
[8] Faller P. Copper in Alzheimer disease: too much, too little, or misplaced? [J]. Free Radic Biol Med, 2012, 52: 747-748.
[9] Rose F, Hodak M, Bernholc J. Mechanism of copper (II)-induced misfolding of Parkinson's disease protein [J]. Sci Rep, 2011, doi: 10.1038/srep00011.
[10] Bush AI, Tanzi RE. Therapeutics for Alzheimer's disease based on the metal hypothesis [J]. Neurotherapeutics, 2008, 5: 421-432.
[11] Madsen E, Gitlin JD. Copper and iron disorders of the brain [J]. Annu Rev Neurosci, 2007, 30: 317-337.
[12] Zhang Y, Zhu JM, Liu CL. Cu2+ and Zn2+-induced aggregation of amyloid-β peptide [J]. Acta Pharm Sin (药学学报), 2012, 47: 399-404.
[13] Singh I, Sagare AP, Coma M, et al. Low levels of copper disrupt brain amyloid-beta homeostasis by altering its production and clearance [J]. Proc Natl Acad Sci USA, 2013, 110: 14771-14776.
[14] Acevedo KM, Hung YH, Dalziel AH, et al. Copper promotes the trafficking of the amyloid precursor protein [J]. J Biol Chem, 2011, 286: 8252-8262.
[15] Hung YH, Robb EL, Volitakis I, et al. Paradoxical condensation of copper with elevated beta-amyloid in lipid rafts under cellular copper deficiency conditions: implications for Alzheimer disease [J]. J Biol Chem, 2009, 284: 21899-21907.
[16] Crapper DR, Krishnan SS, Dalton AJ. Brain aluminum distribution in Alzheimer's disease and experimental neurofi-brillary degeneration [J]. Science, 1973, 180: 511-513.
[17] Perl DP, Brody AR. Alzheimer's disease: X-ray spectrometric evidence of aluminum accumulation in neurofibrillary tangle-bearing neurons [J]. Science, 1980, 208: 297-299.
[18] Yumoto S, Kakimi S, Ohsaki A, et al. Demonstration of aluminum in amyloid fibers in the cores of senile plaques in the brains of patients with Alzheimer's disease [J]. J Inorg Biochem, 2009, 103: 1579-1584.
[19] Bonda DJ, Lee HG, Blair JA, et al. Role of metal dyshomeostasis in Alzheimer's disease [J]. Metallomics, 2011, 3: 267-270.
[20] Pohanka M. Copper, aluminum, iron and calcium inhibit human acetylcholinesterase in vitro [J]. Environ Toxicol Pharmacol, 2014, 37: 455-459.
[21] Xiao F, Li XG, Zhang XY, et al. Combined administration of D-galactose and aluminium induces Alzheimer like lesions in brain [J]. Neurosci Bull, 2011, 27: 143-155.
[22] Ribes D, Colomina MT, Vicens P, et al. Effects of oral aluminum exposure on behavior and neurogenesis in a transgenic mouse model of Alzheimer's disease [J]. Exp Neurol, 2008, 214: 293-300.
[23] Ribes D, Torrente M, Vicens P, et al. Recognition memory and beta-amyloid plaques in adult Tg2576 mice are not modified after oral exposure to aluminum [J]. Alzheimer Dis Assoc Disord, 2012, 26: 179-185.
[24] González-Domínguez R, García-Barrera T, Gómez-Ariza JL. Homeostasis of metals in the progression of Alzheimer's disease [J]. Biometals, 2014, 27: 539-549.
[25] Rembach A, Hare DJ, Doecke JD, et al. Decreased serum zinc is an effect of ageing and not Alzheimer's disease [J]. Metallomics, 2014, 6: 1216-1219.
[26] Brewer GJ. Copper excess, zinc deficiency, and cognition loss in Alzheimer's disease [J]. Biofactors, 2012, 38: 107-113.
[27] Karakas E, Simorowski N, Furukawa H. Structure of the zinc-bound amino-terminal domain of the NMDA receptor NR2B subunit [J]. EMBO J, 2009, 28: 3910-3920.
[28] Takeda A, Iwaki H, Ando M, et al. Zinc differentially acts on components of long-term potentiation at hippocampal CA1 synapses [J]. Brain Res, 2010, 1323: 59-64.
[29] Wenzel HJ, Cole TB, Born DE, et al. Ultrastructural localization of zinc transporter-3 (ZnT-3) to synaptic vesicle membranes within mossy fiber boutons in the hippocampus of mouse and monkey [J]. Proc Natl Acad Sci USA, 1997, 94: 12676-12681.
[30] Religa D, Strozyk D, Cherny RA, et al. Elevated cortical zinc in Alzheimer disease [J]. Neurology, 2006, 67: 69-75.
[31] Lovell MA, Smith JL, Xiong SL, et al. Alterations in zinc transporter protein-1 (ZnT-1) in the brain of subjects with mild cognitive impairment, early, and late-stage Alzheimer's disease [J]. Neurotox Res, 2005, 7: 265-271.
[32] Smith JL, Xiong S, Markesbery WR, et al. Altered expression of zinc transporters-4 and -6 in mild cognitive impairment, early and late Alzheimer's disease brain [J]. Neuroscience, 2006, 140: 879-888.
[33] Adlard PA, Parncutt JM, Finkelstein DI, et al. Cognitive loss in zinc transporter-3 knock-out mice: a phenocopy for the synaptic and memory deficits of Alzheimer's disease? [J]. J Neurosci, 2010, 30: 1631-1636.
[34] Sun XY, Wei YP, Xiong Y, et al. Synaptic released zinc promotes tau hyperphosphorylation by inhibition of protein phosphatase 2A (PP2A) [J]. J Biol Chem, 2012, 287: 11174-11182.
[35] Xiong Y, Jing XP, Zhou XW, et al. Zinc induces protein phosphatase 2A inactivation and tau hyperphosphorylation through Src dependent PP2A (tyrosine 307) phosphorylation [J]. Neurobiol Aging, 2013, 34: 745-756.
[36] Noy D, Solomonov I, Sinkevich O, et al. Zinc-amyloid-beta interactions on a millisecond time-scale stabilize non-fibrillar Alzheimer-related species [J]. J Am Chem Soc, 2008, 130: 1376-1383.
[37] Miller Y, Ma B, Nussinov R. Zinc ions promote Alzheimer Abeta aggregation via population shift of polymorphic states [J]. Proc Natl Acad Sci USA, 2010, 107: 9490-9495.
[38] Wang CY, Wang T, Zheng W, et al. Zinc overload enhances APP cleavage and Abeta deposition in the Alzheimer mouse brain [J]. PLoS One, 2010, 5: e15349.
[39] Zhang X, Li H, Mao Y, et al. An over expression APP model for anti-Alzheimer disease drug screening created by zinc finger nuclease technology [J]. PLoS One, 2013, 8: e75493.
[40] Carlson ES, Magid R, Petryk A, et al. Iron deficiency alters expression of genes implicated in Alzheimer disease pathogenesis [J]. Brain Res, 2008, 1237: 75-83.
[41] Zhu WZ, Zhong WD, Wang W, et al. Quantitative MR phase-corrected imaging to investigate increased brain iron deposition of patients with Alzheimer disease [J]. Radiology, 2009, 253: 497-504.
[42] Brar S, Henderson D, Schenck J, et al. Iron accumulation in the substantia nigra of patients with Alzheimer disease and parkinsonism [J]. Arch Neurol, 2009, 66: 371-374.
[43] Cho HH, Cahill CM, Vanderburg CR, et al. Selective translational control of the Alzheimer amyloid precursor protein transcript by iron regulatory protein-1 [J]. J Biol Chem, 2010, 285: 31217-31232.
[44] Liu B, Moloney A, Meehan S, et al. Iron promotes the toxicity of amyloid beta peptide by impeding its ordered aggregation [J]. J Biol Chem, 2011, 286: 4248-4256.
[45] Wan L, Nie G, Zhang J, et al. beta-Amyloid peptide increases levels of iron content and oxidative stress in human cell and caenorhabditis elegans models of Alzheimer disease [J]. Free Radic Biol Med, 2011, 50: 122-129.
[46] Smith MA, Zhu XW, Tabaton M, et al. Increased iron and free radical generation in preclinical Alzheimer disease and mild cognitive impairment [J]. J Alzheimers Dis, 2010, 19: 363-372.
[47] Suttkus A, Rohn S, Jäger C, et al. Neuroprotection against iron-induced cell death by perineuronal nets — an in vivo analysis of oxidative stress [J]. Am J Neurodegener Dis, 2012, 1: 122-129.
相关文献:
1.张章;俞昌喜.褪黑素对侧脑室注射氯化铝致小鼠学习记忆障碍的改善作用及其机制[J]. 药学学报, 2002,37(9): 682-686