关键词: AIE Alzheimer’s disease amyloid fluorescence lactose near-infrared imaging tetraphenylethylene

Mesh : Mice Animals Alzheimer Disease / metabolism Fluorescent Dyes Solubility Amyloid beta-Peptides / metabolism Mice, Transgenic Amyloidosis Water

来  源:   DOI:10.3390/molecules28135110   PDF(Pubmed)

Abstract:
Alzheimer\'s disease (AD), an amyloid-related disease, seriously endangers the health of elderly individuals. According to current research, its main pathogenic factor is the amyloid protein, which is a kind of fibrillar aggregate formed by noncovalent self-assembly of proteins. Based on the characteristics of aggregation-induced emission (AIE), a bislactosyl-decorated tetraphenylethylene (TPE) molecule TMNL (TPE + malononitrile + lactose), bearing two malononitrile substituents, was designed and synthesized in this work. The amphiphilic TMNL could self-assemble into fluorescent organic nanoparticles (FONs) with near-infrared (NIR) fluorescence emission in physiological PBS (phosphate buffered saline), achieving excellent fluorescent enhancement (47-fold) upon its combination with Aβ1-42 fibrils. TMNL was successfully applied to image Aβ1-42 plaques in the brain tissue of AD transgenic mice, and due to the AIE properties of TMNL, no additional rinsing process was necessary. It is believed that the probe reported in this work should be useful for the sensitive detection and accurate localization mapping of Aβ1-42 aggregates related to Alzheimer\'s disease.
摘要:
阿尔茨海默病(AD),淀粉样蛋白相关疾病,严重危害老年人的健康。根据目前的研究,其主要致病因子是淀粉样蛋白,它是一种由蛋白质非共价自组装形成的纤维状聚集体。基于聚集诱导发射(AIE)的特征,双乳糖基修饰的四苯基乙烯(TPE)分子TMNL(TPE+丙二腈+乳糖),带有两个丙二腈取代基,在这项工作中设计和合成。两亲性TMNL可以在生理PBS(磷酸盐缓冲盐水)中自组装成具有近红外(NIR)荧光发射的荧光有机纳米颗粒(FONs),在与Aβ1-42原纤维组合时实现优异的荧光增强(47倍)。TMNL已成功应用于AD转基因小鼠脑组织中Aβ1-42斑块的成像,由于TMNL的AIE特性,没有额外的冲洗过程是必要的。据信,这项工作中报道的探针对于与阿尔茨海默病相关的Aβ1-42聚集体的灵敏检测和准确定位作图应该是有用的。
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