Simultaneous visualization and quantification of copper (II) ions in Alzheimer's disease by a near-infrared fluorescence probe
Simultaneous visualization and quantification of copper (II) ions in Alzheimer's disease by a near-infrared fluorescence probe
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通过近红外荧光探针同时可视化和定量阿尔茨海默病中的铜 (II) 离子
DOI：
10.1016/j.bios.2021.113858
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发表时间：
2022
影响因子：
12.6
通讯作者：
Haitao Li
中科院分区：
文献类型：
--
作者：
Zile Zhou;Shengyou Chen;Yinghui Huang;Biao Gu;Jiaqi Li;Cuiyan Wu;Peng Yin;Youyu Zhang;Haitao Li
铜离子（Cu 2+）的异常蓄积被认为是阿尔茨海默病（AD）的病理因素之一，但Cu 2+与AD进展的内在关系尚不完全清楚。本工作设计了一种灵敏、选择性强的近红外荧光铜离子探针（DDP-Cu），用于检测AD患者的细胞裂解液、活细胞、活斑马鱼以及果蝇和小鼠脑组织中的Cu ~（2+）水平。通过使用该探针，我们证明了AD小鼠和果蝇脑中Cu 2+的含量分别比正常小鼠和果蝇增加了近3.5倍和4倍。更重要的是，发病机制分析显示，Cu 2+升高导致与AD密切相关的因素发生变化，如活性氧（ROS）增加、β淀粉样蛋白（Aβ）聚集和神经细胞毒性。这些发现有助于加深对Cu ~（2+）与AD关系的认识。
The abnormal accumulation of copper ions (Cu2+) is considered to be one of the pathological factors of Alzheimer's disease (AD), but the internal relationship between Cu2+and AD progression is still not fully clear. In this work, a sensitive and selective near-infrared fluorescent copper ion probe (DDP-Cu) was designed for quantification and visualization of Cu2+level in lysates, living cells, living zebrafish and brain tissues of drosophila and mice with AD. By using this probe, we demonstrated that the content of Cu2+in the brains of AD mice and drosophila enhanced nearly 3.5-fold and 4-fold than that of normal mice and drosophila, respectively. More importantly, pathogenesis analysis revealed that elevated Cu2+led to changes in factors closely associated with AD, such as the increasing of reactive oxygen species(ROS), the aggregation of amyloid-β protein (Aβ) and nerve cell cytotoxicity. These findings could promote the understanding of the roles between Cu2+and AD.