阿尔茨海默病(AD)是一类在老年人中发病率很高的神经退行性疾病，在AD病人的脑部区域常伴有金属离子介导的β-淀粉样蛋白(Aβ)的聚集和纤维化以及金属硫蛋白（MT）的下调。研究MT对Aβ的聚集及其神经元细胞毒性的抑制作用对于深入理解MT在AD症的形成、发展以及治疗领域所起的作用具有十分重要的意义。本项目拟采用电化学相关技术辅助硫磺素(ThT)荧光分析、原子力显微镜（AFM）以及圆二色光谱（CD）技术研究不同亚型Zn7-MT对Cu介导Aβ聚集的抑制作用，并以N2a 和PC12细胞株为研究对象，借助 MTT 法、溶出伏安法、石墨炉原子吸收法以及3-CCA 荧光探针法研究不同亚型Zn7-MT对Aβ-Cu神经元细胞毒性的抑制作用。本项目的实施将进一步拓宽新型生物传感技术的应用领域并有助于对MT在AD的病理及毒理研究中所起的重要作用进行更深入的了解。

Alzheimer's disease (AD) is one of the most common neurodegenerative diseases, with a high incidence among elderly people. Metals ion mediated accumulation/fibrosis of amyloid beta protein (Aβ), decreased level of metallothionein(MT) often occurs in the brain of AD patients. Studies on the inhibitory effect of MT on the aggregation and neurotoxicity on Aβ will further understanding the role of MT in the formation, development and treatment process of AD. We intend to adopt an electrochemical technology assisted with Thioflavin fluorescence analysis (ThT), atomic force microscopy (AFM) and circular dichroism (CD)spectrum technique to study the inhibition effects of different subtypes of Zn7-MT on Cu mediated Aβ aggregation. Meanwhile, taken N2a and PC12 cell lines as research objects to study the inhibition effects of different subtypes of Zn7-MT on the neurotoxicity of Aβ-Cu by the aid of MTT assay, stripping voltammetry, graphite furnace atomic absorption spectrometry and 3-CCA fluorescence probe methods. The implementation of this project will be further widen the application area of biosensing techniche, also helps us to understand the unrevealed function of MT on the pathology and toxicology of AD.