GFP-based red-emissive fluorescent probes for dual imaging of β-amyloid plaques and mitochondrial viscosity.
GFP-based red-emissive fluorescent probes for dual imaging of β-amyloid plaques and mitochondrial viscosity.
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DOI：
10.1016/j.bioorg.2023.106540
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发表时间：
2023-04
影响因子：
5.1
通讯作者：
Huaxiang Leng;Jinrong Yang;Liansheng Long;Yiyong Yan;Wenbin Shi;Lei Zhang;Jin-wu Yan
中科院分区：
文献类型：
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作者：
Huaxiang Leng;Jinrong Yang;Liansheng Long;Yiyong Yan;Wenbin Shi;Lei Zhang;Jin-wu Yan
阿尔茨海默病（Alzheimer's disease，AD）是一种神经退行性疾病，具有不可治愈的特点，寻找更好的AD早期诊断生物标志物已成为AD研究的热点。在众多的生物标志物中，β淀粉样蛋白（Aβ）聚集体和线粒体粘度与AD密切相关，二者的双重显像可能为AD的诊断提供一种潜在可行的策略。本研究设计并合成了5种基于绿色荧光蛋白的红色荧光探针，用于选择性检测β-淀粉样蛋白斑块和线粒体粘度，其中C25 e具有上级性质，可成功地对β-淀粉样蛋白斑块和线粒体粘度进行成像，其荧光波长信号分别在624和640 nm附近“开启”。此外，转基因AD小鼠脑切片染色显示，探针C25对Aβ斑块显示出比市售Thio-S更高的选择性和信噪比。此外，还首次将探针C25 e用于检测淀粉样蛋白诱导的线粒体粘度变化。因此，基于GFP的红色荧光探针C25 e可以作为一种双功能的工具，用于β-淀粉样蛋白斑块和线粒体粘度的成像，这可能为阿尔茨海默病的早期诊断提供一种独特的策略。
Alzheimer’s disease (AD), with incurable neurodegenerative damage, has attracted growing interest in exploration of better AD biomarkers in its early diagnosis. Among various biomarkers, amyloid-β (Aβ) aggregates and mitochondrial viscosity are closely related to AD and their dual imaging might provide a potential and feasible strategy. In this work, five GFP-based red-emissive fluorescent probes were rationally designed and synthesized for selective detection of β-amyloid plaques and viscosity, among whichC25eexhibited superior properties and could successfully image β-amyloid plaques and mitochondrial viscosity with different fluorescence wavelength signals “turn-on” at around 624 and 640 nm, respectively. Moreover, the staining of brain sections from a transgenic AD mouse showed that probeC25eshowed higher selectivity and signal-to-noise ratio towards Aβ plaques than commercially-available Thio-S. In addition, the probeC25ewas, for the first time, employed for monitoring amyloid-β induced mitochondrial viscosity changes. Therefore, this GFP-based red-emissive fluorescent probeC25ecould serve as a dual-functional tool for imaging β-amyloid plaques and mitochondrial viscosity, which might provide a unique strategy for the early diagnosis of Alzheimer’s disease.