Department of Chemistry, University of Rochester, Rochester, New York 14627-0216, United States.
Department of Biochemistry and Biophysics, University of Rochester Medical Center, Rochester, New York 14642, United States.
ACS Chem Neurosci. 2024 Sep 4;15(17):3124-3135. doi: 10.1021/acschemneuro.4c00183. Epub 2024 Aug 15.
Various oligomeric species of amyloid-beta have been proposed to play different immunogenic roles in the cellular pathology of Alzheimer's Disease. The dynamic interconversion between various amyloid oligomers and fibrillar assemblies makes it difficult to elucidate the role each potential aggregation state may play in driving neuroinflammatory and neurodegenerative pathology. The ability to identify the amyloid species that are key and essential drivers of these pathological hallmarks of Alzheimer's Disease is of fundamental importance for also understanding downstream events including tauopathies that mediate neuroinflammation with neurologic deficits. Here, we report the design and construction of a quantum dot mimetic for larger spherical oligomeric amyloid species as an "endogenously" fluorescent proxy for this cytotoxic assembly of amyloid to investigate its role in inducing inflammatory and stress response states in neuronal and glial cell types. The design parameters and construction protocol developed here may be adapted for developing quantum dot nano-bio assemblies for other biological systems of interest, particularly neurodegenerative diseases involving other protein aggregates.
各种淀粉样β寡聚体被认为在阿尔茨海默病的细胞病理学中发挥不同的免疫原性作用。淀粉样寡聚体和纤维状组装体之间的动态相互转化使得难以阐明每种潜在聚集状态在驱动神经炎症和神经退行性病理中的作用。能够识别出这些淀粉样物质是阿尔茨海默病病理特征的关键和基本驱动因素，对于理解包括介导神经炎症和神经功能缺损的tau 病在内的下游事件也具有重要意义。在这里，我们报告了一种量子点模拟物的设计和构建，用于较大的球形寡聚淀粉样物质，作为这种细胞毒性淀粉样组装的内源性荧光代理，以研究其在诱导神经元和神经胶质细胞类型的炎症和应激反应状态中的作用。这里开发的设计参数和构建方案可以适应用于其他感兴趣的生物系统的量子点纳米生物组装，特别是涉及其他蛋白质聚集的神经退行性疾病。
