Optical control of tau aggregation to model Alzheimer's disease in human neurons

项目总结 阿尔茨海默病(AD)是最常见的神经退行性疾病，其病理特点是 通过沉积β-淀粉样蛋白和tau积聚，导致广泛的神经元丢失。汇聚的证据 来自体内和体外的研究支持tau蛋白及其聚集的异常行为起到了 在阿尔茨海默病病理发展中的中心作用，但还没有实验方法来 以极高的时间和空间精度控制tau聚集。为了解决这个根本问题，我们有 开发了一种新的合成技术来光学控制致病蛋白在光下的聚集 照明。我们建议使用这种方法来控制tau聚集，以便用人类来模拟AD 多能干细胞(HiPSCs)来源的神经元。在未来，我们建议的研究将补充 现有的动物模型，为药物筛选/验证提供了一个新的平台。牛磺酸的光学控制 聚合将把当前的疾病建模和药物筛选概念转变为创新 翻译方法。

PROJECT SUMMARY Alzheimer's disease (AD) is the most common neurodegenerative disease and its pathology is characterized by deposition of β-amyloid and tau accumulations, leading to extensive neuron loss. The converging evidence from in vivo and in vitro studies support that aberrant behaviors of tau protein and their aggregation play a central role in the development of Alzheimer's disease pathology, but there is no experimental approach to control tau aggregation with great temporal and spatial precision. To address this fundamental issue, we have developed a new synthetic technique to optically control aggregation of pathogenic proteins upon light illumination. We propose to use this approach to control tau aggregation in order to model AD with human pluripotent stem cells (hiPSCs)-derived neurons. In future, our proposed studies will be complementary to existing animal models, and providing a novel platform for drug screening/validation. The optical control of tau aggregation will transform the current concepts of disease modeling and drug screening toward innovative translational approaches.