Selective In Vitro and Ex Vivo Staining of Brain Neurofibrillary Tangles and Amyloid Plaques by Novel Ethylene Ethynylene-Based Optical Sensors.
Selective In Vitro and Ex Vivo Staining of Brain Neurofibrillary Tangles and Amyloid Plaques by Novel Ethylene Ethynylene-Based Optical Sensors.
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DOI：
10.3390/bios13020151
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发表时间：
2023-01-18
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鉴定蛋白质聚集体作为神经变性的生物标志物是疾病诊断和治疗开发的感兴趣的领域。在这项工作中，我们提出了新的超发光共轭双链分子作为离体传感器的tau配对螺旋丝（PHF）和淀粉样蛋白-β（Aβ）斑块。我们评估了两种寡聚对亚苯基乙炔（OPEs），阴离子OPE 12 −和阳离子OPE 24+，作为阿尔茨海默病（AD）tau蛋白病转基因小鼠（rTg 4510）和大鼠（TgF 344-AD）模型脑切片和人额颞叶痴呆（FTD）尸检脑切片中纤维蛋白病理学的染色剂的使用。OPE 12 −在荧光测定中显示出对PHF的选择性，并对小鼠和人脑组织切片中的神经纤维缠结（NFT）进行了强染色，而OPE 24+对NFT和Aβ斑块进行了染色。两种OPEs均以有限的背景或非特异性染色对脑切片进行染色。这种新型传感器家族在传感能力方面优于金标准染料硫磺素T，并与传统的磷酸化tau（AT 180）和Aβ（4G 8）抗体共染色。由于OPEs容易在体外和离体结合蛋白质淀粉样蛋白，因此它们是用于鉴定与AD相关的蛋白质病理性包涵体的选择性和快速工具。这样的OPEs可以是有用的，在了解发病机制，并在创建体内诊断相关的检测工具，神经退行性疾病。
The identification of protein aggregates as biomarkers for neurodegeneration is an area of interest for disease diagnosis and treatment development. In this work, we present novel super luminescent conjugated polyelectrolyte molecules as ex vivo sensors for tau-paired helical filaments (PHFs) and amyloid-β (Aβ) plaques. We evaluated the use of two oligo-p-phenylene ethynylenes (OPEs), anionic OPE12− and cationic OPE24+, as stains for fibrillar protein pathology in brain sections of transgenic mouse (rTg4510) and rat (TgF344-AD) models of Alzheimer’s disease (AD) tauopathy, and post-mortem brain sections from human frontotemporal dementia (FTD). OPE12− displayed selectivity for PHFs in fluorimetry assays and strong staining of neurofibrillary tangles (NFTs) in mouse and human brain tissue sections, while OPE24+ stained both NFTs and Aβ plaques. Both OPEs stained the brain sections with limited background or non-specific staining. This novel family of sensors outperformed the gold-standard dye Thioflavin T in sensing capacities and co-stained with conventional phosphorylated tau (AT180) and Aβ (4G8) antibodies. As the OPEs readily bind protein amyloids in vitro and ex vivo, they are selective and rapid tools for identifying proteopathic inclusions relevant to AD. Such OPEs can be useful in understanding pathogenesis and in creating in vivo diagnostically relevant detection tools for neurodegenerative diseases.
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影响因子：
6.1
作者：
Combs B;Hamel C;Kanaan NM
通讯作者：
Kanaan NM
寡苯基乙烯乙烯荧光传感器和Aβ低聚物的结合动力学的计算研究。
影响因子：
5
作者：
Martin TD;Brinkley G;Whitten DG;Chi EY;Evans DG
通讯作者：
Evans DG
影响因子：
15.1
作者：
Do Carmo S;Cuello AC
通讯作者：
Cuello AC
影响因子：
4
作者：
Castillo-Carranza, Diana L.;Gerson, Julia E.;Kayed, Rakez
通讯作者：
Kayed, Rakez
影响因子：
5.6
作者：
Davidson, Darcy S.;Brown, Anne M.;Lemkul, Justin A.
通讯作者：
Lemkul, Justin A.