权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

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

光学控制 tau 蛋白聚集来模拟人类神经元中的阿尔茨海默病

基本信息

批准号：
9902299
负责人：
Gabsang Lee
金额：
$ 16.38万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-04-01 至 2022-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9902299
关键词：
Address Affect Alzheimer&apos s Disease Alzheimer&apos s disease brain Alzheimer&apos s disease model Alzheimer&apos s disease pathology Amyloid beta-Protein Animal Model Astrocytes Behavior Biological CRISPR/Cas technology Caenorhabditis elegans Cell Death Cell Line Dementia Development Disease Progression Disease model Drug Screening Exhibits Frequencies Future Hour Human In Vitro Inflammatory Response Knock-in Light Lighting Mediating Memory impairment Modeling Molecular Mouse-ear Cress Names Nerve Degeneration Neurodegenerative Disorders Neurofibrillary Tangles Neurons Optics Oxidative Stress Pathogenesis Pathogenicity Pathologic Pathology Phenotype Photosensitivity Play Prions Process Prosencephalon Proteins Regimen Reporting Rodent Model Role Senile Plaques Series Synapses System Techniques Technology Testing Therapeutic Time Toxic effect Transgenic Organisms Validation abeta accumulation abeta deposition cell behavior cell type cryptochrome 2 drug discovery experimental study human pluripotent stem cell hyperphosphorylated tau in vivo inhibitor/antagonist innovation light intensity mitochondrial dysfunction molecular phenotype monomer mouse model nervous system disorder neurofibrillary tangle formation neuron loss new technology novel paired helical filament protein TDP-43 protein aggregation response spatiotemporal tau Proteins tau aggregation tau mutation tau phosphorylation tool translational approach

项目摘要

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.

项目摘要阿尔茨海默病（Alzheimer's disease，AD）是最常见的神经退行性疾病，其病理特征是通过β-淀粉样蛋白和tau蛋白的沉积，导致广泛的神经元损失。汇聚的证据来自体内和体外的研究支持tau蛋白的异常行为和它们的聚集起作用，在阿尔茨海默病病理学的发展中起核心作用，但没有实验方法来以极大的时间和空间精度控制tau聚集。为了解决这个根本问题，我们开发了一种新的合成技术，以光学方式控制致病蛋白质在光下的聚集照明。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（hiPSC）衍生的神经元。今后，我们建议的研究将与以下方面相辅相成：现有的动物模型，并为药物筛选/验证提供新的平台。tau的光学控制聚合将改变目前的疾病建模和药物筛选的概念，翻译方法