Department of Chemistry, Korea University, Seoul 02841, Korea.
Chem Soc Rev. 2018 Apr 3;47(7):2249-2265. doi: 10.1039/c7cs00706j.
Historically, in Alzheimer's disease research, a lot of attention has been paid to the development of highly selective fluorophores for beta amyloid plaques. With a shift in the understanding of the disease and the importance of a network of cross-talk interactions, the development of small-molecule fluorescent dyes with high selectivity for (hyperphosphorylated) tau protein aggregates in neurofibrillary tangles has been gaining increasing attention. Fluorescent dyes for the selective labelling of tau aggregates in histological AD brain sections have been described, spanning the entire visible range of the electromagnetic spectrum. Despite the relatively early stages of the development of the field, a large diversity in probe architectures has been reported. Importantly, a handful of near-infrared-emissive dyes have been described as well, and some of these have exhibited good pharmacological profiles, with a significant blood-brain-barrier permeability, and a demonstrated ability to label tau tangles in vivo in small-animal models of Alzheimer's disease and other tauopathies. The developments summarized in the current work are expected to aid the unravelling of the diverse set of players in the etiology of Alzheimer's disease. In this tutorial review, we seek to provide the reader with an overview of the most important recent developments and hope to provide some guidelines for the design of future probes.
从历史上看，在阿尔茨海默病研究中，人们非常关注开发高选择性荧光团来检测β淀粉样斑块。随着对疾病的认识的转变以及对相互作用网络重要性的认识，人们越来越关注开发对神经纤维缠结中（过度磷酸化的）tau 蛋白聚集体具有高选择性的小分子荧光染料。已经描述了用于选择性标记 AD 脑切片中 tau 聚集体的荧光染料，涵盖了整个电磁光谱的可见范围。尽管该领域的发展相对较早，但已经报道了探针结构的多样性。重要的是，也已经描述了一些近红外发射染料，其中一些具有良好的药理学特性，具有显著的血脑屏障通透性，并证明能够在阿尔茨海默病和其他 tau 病的小动物模型中体内标记 tau 缠结。当前工作中总结的发展有望帮助揭示阿尔茨海默病发病机制中多样化的参与者。在本教程综述中，我们试图为读者提供最近最重要的发展概述，并希望为未来探针的设计提供一些指导。
