Fluoro-substituted cyanine for reliable in vivo labelling of amyloid-β oligomers and neuroprotection against amyloid-β induced toxicity.
Fluoro-substituted cyanine for reliable in vivo labelling of amyloid-β oligomers and neuroprotection against amyloid-β induced toxicity.
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氟取代的花青可用于可靠的体内标记淀粉样蛋白 B 寡聚物和针对淀粉样蛋白 B 诱导的毒性的神经保护
DOI：
10.1039/c7sc03974c
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发表时间：
2017-12-01
期刊：
影响因子：
8.4
通讯作者：
Wong MS
中科院分区：
文献类型：
--
作者：
Li Y;Xu D;Sun A;Ho SL;Poon CY;Chan HN;Ng OTW;Yung KKL;Yan H;Li HW;Wong MS
报道了一种新型的治疗诊断剂--氟代花菁，它能在体内可靠地标记Aβ寡聚体，并对Aβ诱导的毒性有较强的神经保护作用，可用于阿尔茨海默病的早期诊断和治疗。阿尔茨海默病（AD）是最普遍但仍然无法治愈的神经退行性痴呆形式。早期诊断和干预对于延迟疾病的发作和进展至关重要。本文报道了一种新的氟取代花菁F-SLOH，它具有良好的Aβ寡聚体选择性和高结合亲和力，这归因于强π-π堆积和分子间CH···O和CH···F相互作用的协同效应。通过在组织切片上进行体外标记以及通过在7个月APP/PS1双转基因（Tg）和APP/PS1/Tau三转基因小鼠模型中全身给予F-SLOH进行体内标记，确定了对大脑中Aβ寡聚体的选择性。F-SLOH还显示出显著有效的抑制Aβ聚集和高度期望的神经保护作用，包括抑制ROS产生和Ca 2+内流。其优异的血脑屏障（BBB）穿透性和低生物毒性进一步支持其作为AD早期诊断和治疗的新型治疗诊断剂的巨大潜力。
A fluoro-substituted cyanine showing reliable in vivo labelling of Aβ oligomers and potent neuroprotective effect against Aβ-induced toxicities is reported as a novel theranostic agent for the early diagnosis and therapy of Alzheimer's disease. Alzheimer’s disease (AD) is the most prevalent but still incurable neurodegenerative form of dementia. Early diagnosis and intervention are crucial for delaying the onset and progression of the disease. We herein report a novel fluoro-substituted cyanine, F-SLOH, which exhibits good Aβ oligomer selectivity with a high binding affinity, attributed to the synergistic effect of strong π–π stacking and intermolecular CH···O and CH···F interactions. The selectivity towards the Aβ oligomers in the brain was ascertained by in vitro labelling on tissue sections and in vivo labelling through the systemic administration of F-SLOH in 7 month APP/PS1 double transgenic (Tg) and APP/PS1/Tau triple Tg mouse models. F-SLOH also shows remarkably effective inhibition on Aβ aggregation and highly desirable neuroprotective effects against Aβ-induced toxicities, including the inhibition of ROS production and Ca2+ influx. Its excellent blood–brain barrier (BBB) penetrability and low bio-toxicity further support its tremendous potential as a novel theranostic agent for both early diagnosis and therapy of AD.
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影响因子：
14
作者：
Li, Yinhui;Xu, Di;Wong, Man Shing
通讯作者：
Wong, Man Shing
影响因子：
38.3
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影响因子：
64.5
作者：
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通讯作者：
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影响因子：
15
作者：
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通讯作者：
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影响因子：
16.6
作者：
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通讯作者：
Wong, Man Shing