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    题名 作者 年代 出处 被引量
1Tau蛋白介导阿尔兹海默病的机理及相关药物显示文摘阿尔兹海默症是一种以智力缓慢丧失为特征的神经退行性疾病,主要病理特征之一为神经细胞内出现大量神经纤维缠结.神经纤维缠结的主要成分为异常磷酸化的Tau蛋白,研究Tau蛋白的结构和功能以及神经纤维缠结形成的分子机制具有重要的生理意义.Tau和Aβ是阿尔兹海默病药物开发的两个重要靶点,随着近期一些以Aβ为靶点的药物临床研究宣告失败,越来越多的研究组已经开始考虑改变研发阿尔兹海默病药物的策略,并开始转向以Tau为靶点的药物开发.本文综述了Tau介导阿尔兹海默病的机理及相关药物的研究进展.刘鹏 赵玉芬 李艳梅 2010中国科学:化学2010,40,7:14
2脑锌代谢与阿尔茨海默病显示文摘锌是中枢神经系统含量最丰富的过渡金属元素之一,对维持中枢神经系统正常生理功能具有重要作用,其稳态失衡与多种疾病有关。阿尔茨海默病是一种多病因神经退行性疾病,以β-淀粉样斑块形成和神经原纤维缠结为主要病理特征。研究表明,脑锌代谢紊乱在阿尔茨海默病发病过程中扮演重要角色,但确切机制尚不十分清楚。综述了脑锌代谢和稳态调控以及锌和锌转运蛋白参与β-淀粉样蛋白沉积与老年斑形成的病理过程,并探讨了金属-蛋白阻尼复合物如何通过恢复脑锌稳态延缓疾病进程、改善患者认知能力的治疗策略。郑玮 王占友 2012生命科学2012,24,8:11
3Modulation of tau phosphorylation by environmental copper显示文摘Background:The transition metal copper enhances amyloidβaggregation and neurotoxicity,and in models of concomitant amyloid and tau pathology,copper also promotes tau aggregation.Since it is not clear if the effects of environmental copper upon tau pathology are dependent on the presence of pathological amyloidβ,we tested the effects of copper overload and complexing in disease models which lack pathological amyloidβ.Methods:We used cell culture and transgenic murine models to test the effects of environmental copper on tau phosphorylation.We used oral zinc acetate as a copper lowering agent in mice and examined changes in blood and brain metals through inductively coupled plasma mass spectroscopy.Behavioral effects of copper lowering were assessed with Morris water maze and novel object recognition tasks.Changes in tau phosphorylation were examined by phosphorylation specific antibodies on Western blots.Results:In human neuroblastoma cells,excess copper promoted tau phosphorylation and a copper complexing agent,tetrathiomolybdate,attenuated tau phosphorylation.In a transgenic mouse model expressing wild type human tau,copper-lowering by oral zinc suppressed plasma and brain levels of copper,and resulted in a marked attenuation of tau phosphorylation.No significant changes in behavior were observed with copper lowering,but a trend to improved recognition of the novel object was observed in zinc acetate treated mice.Conclusions:We propose that reduction of brain copper by blocking uptake of copper from the diet may be a viable strategy for modulating tau pathology in Alzheimer’s disease.The potential benefits of this approach are tempered by the absence of a behavioral benefit and by the health risks of excessive lowering of copper.Kellen Voss Christopher Harris Martina Ralle Megan Duffy Charles Murchison Joseph F Quinn 2014Translational Neurodegeneration2014,3,1:3
4铜稳态对铁代谢平衡的影响显示文摘铜是人体必需的微量元素,参与体内多种蛋白和酶的组成,机体内存在严格的铜稳态调控机制。作为血浆中最主要的多铜亚铁氧化酶——铜蓝蛋白,与另外两种同源亚铁氧化酶——膜铁转运辅助蛋白和zyklopen,共同参与体内铁的转运,维持铁代谢的平衡。将对调节铜和铁平衡的重要意义以及铜和铁在机体代谢过程中的相互作用、发展动态进行讨论。郭飞龙 姜瑞伟 陈惠君 2012生命科学2012,24,8:2
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