Protein aggregation has been widely implicated in neurodegenerative diseases such as Alzheimer’s disease, frontotemporal dementia, Parkinson’s disease, and Huntington disease, as well as in systemic amyloidoses and conditions associated with localized amyloid deposits, such as type-II diabetes. The pressing need for a better understanding of the factors governing protein assembly has driven research for the development of molecular sensors for amyloidogenic proteins. To date, a number of sensors have been developed that report on the presence of protein aggregates utilizing various modalities, and their utility demonstrated for imaging protein aggregation in vitro and in vivo. Analysis of these sensors highlights the various advantages and disadvantages of the different imaging modalities and makes clear that multimodal sensors with properties amenable to more than one imaging technique need to be developed. This critical review highlights the key molecular scaffolds reported for molecular imaging modalities such as fluorescence, positron emission tomography, single photon emission computed tomography, and magnetic resonance imaging and includes discussion of the advantages and disadvantages of each modality, and future directions for the design of amyloid sensors. We also discuss the recent efforts focused on the design and development of multimodal sensors and the value of cross-validation across multiple modalities.

中文翻译：

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淀粉样蛋白分子成像的策略和多峰方法的价值。

蛋白质聚集已广泛涉及神经退行性疾病，例如阿尔茨海默氏病，额颞痴呆，帕金森氏病和亨廷顿病，以及全身性淀粉样蛋白和与局部淀粉样蛋白沉积有关的疾病，例如II型糖尿病。迫切需要更好地了解控制蛋白质组装的因素，这推动了淀粉样蛋白蛋白质分子传感器的开发研究。迄今为止，已经开发出许多传感器，它们利用各种方式报告蛋白质聚集体的存在，并证明了其在体外和体内成像蛋白质聚集体的实用性。对这些传感器的分析突出显示了不同成像方式的各种优点和缺点，并明确指出，需要开发具有适合多种成像技术的特性的多峰传感器。这篇重要的评论着重介绍了分子成像方式（例如荧光，正电子发射断层扫描，单光子发射计算机断层扫描和磁共振成像）所报道的关键分子支架，并讨论了每种方式的优缺点，以及未来的设计方向。淀粉样蛋白传感器。我们还将讨论最近针对多模式传感器的设计和开发以及跨多种模式的交叉验证的价值所做的努力。