PDF(Pubmed)
Abstract：
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.
摘要：
已经提出淀粉样β的各种寡聚物种在阿尔茨海默病的细胞病理学中起不同的免疫原性作用。各种淀粉样蛋白寡聚体和原纤维组件之间的动态相互转化使得难以阐明每种潜在的聚集状态可能在驱动神经炎性和神经变性病理学中起的作用。识别淀粉样蛋白是阿尔茨海默病这些病理标志的关键和基本驱动因素的能力对于理解下游事件，包括介导神经炎症和神经缺陷的tau蛋白病也是至关重要的。这里,我们报道了一种量子点模拟物的设计和构建，用于较大的球形淀粉样蛋白寡聚物，作为淀粉样蛋白细胞毒性组装的“内源性”荧光代表，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。此处开发的设计参数和构造协议可以适用于开发用于其他感兴趣的生物系统的量子点纳米生物组件。特别是涉及其他蛋白质聚集体的神经退行性疾病。
