Aluminum induces neurodegeneration and its toxicity arises from increased iron accumulation and reactive oxygen species (ROS) production

被引:142
作者
Wu, Zhihao [1 ]
Du, Yumei [1 ]
Xue, Hua [1 ]
Wu, Yongsheng [1 ]
Zhou, Bing [1 ]
机构
[1] Tsinghua Univ, State Key Lab Biomembrane & Membrane Biotechnol, Sch Life Sci, Beijing 100084, Peoples R China
关键词
Al; AD (Alzheimer's disease); Iron dyshomeostasis; ROS; MITOCHONDRIAL ENERGY-METABOLISM; HYDROGEN-PEROXIDE; OXIDATIVE STRESS; DROSOPHILA MODEL; RAT-BRAIN; IN-VITRO; SUPEROXIDE; CHAPERONE; FRATAXIN; SUSCEPTIBILITY;
D O I
10.1016/j.neurobiolaging.2010.06.018
中图分类号
R592 [老年病学]; C [社会科学总论];
学科分类号
03 ; 0303 ; 100203 ;
摘要
The neurotoxicity of aluminum (Al) - the most abundant metal element on earth - has been known for years. However, the mechanism of Al-induced neurodegeneration and its relationship to Alzheimer's disease are still controversial. In particular, in vivo functional data are lacking. In a Drosophila model with chronic dietary Al overloading, general neurodegeneration and several behavioral changes were observed. Al-induced neurodegeneration is independent of beta-amyloid or tau-associated toxicity, suggesting they act in different molecular pathways. Interestingly, Drosophila frataxin (dfh), which causes Friedreich's ataxia if mutated in humans, displayed an interacting effect with Al, suggesting Friedreich's ataxia patients might be more susceptible to Al toxicity. Al-treated flies accumulated large amount of iron and reactive oxygen species (ROS), and exhibited elevated SOD2 activity. Genetic and pharmacological efforts to reduce ROS or chelate excess Fe significantly mitigated Al toxicity. Our results indicate that Al toxicity is mediated through ROS production and iron accumulation and suggest a remedial route to reduce toxicity due to Al exposure. (C) 2012 Elsevier Inc. All rights reserved.
引用
收藏
页码:199.e1 / 199.e12
页数:12
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