硫酸乙酰肝素 3-O-硫酸化在阿尔茨海默氏病 Tau 蛋白病跨细胞传播中的作用-猫眼课题宝

硫酸乙酰肝素 3-O-硫酸化在阿尔茨海默氏病 Tau 蛋白病跨细胞传播中的作用

批准号：

10054740

负责人：

ROBERT J LINHARDT

金额：

$259.51万

依托单位：

RENSSELAER POLYTECHNIC INSTITUTE

依托单位国家：

美国

项目类别：

财政年份：

2020

资助国家：

美国

项目状态：

已结题

起止时间：

2020-09-15 至 2024-08-31

来源：

https://reporter.nih.gov/project-details/10054740

关键词：

Alzheimer&apos s Disease Alzheimer&apos s disease brain Alzheimer&apos s disease therapy Animal Model Animals Binding Biosensor Brain Cell Culture Techniques Cell Line Cell surface Cells Chemicals Clustered Regularly Interspaced Short Palindromic Repeats Complex Core Protein Data Dementia Disaccharides Disease Drug Design Enzymes Fluorescence Resonance Energy Transfer Future Glucosamine Glucuronic Acids Goals Heparan Sulfate Proteoglycan Heparitin Sulfate Hippocampus (Brain)Human Iduronic Acid Impaired cognition Injections Link MAPT gene Mass Spectrum Analysis Mediating Methods Microtubule Stabilization Microtubules Modification Molecular Movement Mutagenesis Neurofibrillary Tangles Neurons Oligosaccharides Pathogenesis Pathologic Pathology Pattern Pharmaceutical Preparations Physiology Play Polysaccharides Proteins Public Health Relaxation Role Signal Transduction Small Interfering RNA Staging Structure Sulfate Surface Tauopathies Testing Translating Uronic Acids Work base cell type design drug development drug discovery hTau Mice inhibitor/antagonist insight migration mimetics molecular dynamics mouse genetics mouse model neural network novel overexpression prion-like protein aggregation role model structural biology sulfotransferase tau Proteins tau aggregation tau interaction tool uptake

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中文摘要

翻译

神经元缠结（NFT）是阿尔茨海默病（AD）的一个病理标志。NFT由以下组成聚集的tau蛋白，并且与痴呆进展中的认知下降相关。NFT在大脑中传播以朊病毒样的方式，由tau蛋白和神经元表面聚糖之间的相互作用介导。长期目标是研究tau-聚糖相互作用的结构细节，并发现破坏这种相互作用的药物用于改善AD的疾病治疗。在这个提议中，我们将研究tau-硫酸乙酰肝素相互作用，在分子（目标1）、细胞（目标2）和生物体水平上进行药物发现（目标3）。

英文摘要

Neurofibrillary tangles (NFT) is a pathological hallmark of Alzheimer’s disease (AD). NFT is composed of aggregated tau protein and is correlated to cognitive decline in dementia progression. NFT spreads in the brain in a prion-like manner, mediated by the interaction between tau and neuronal surface glycans. The long-term goal is to study the structural details of tau-glycan interaction and to discover drugs to disrupt this interaction for disease-modifying treatment of AD. In this proposal, we will study the tau-heparan sulfate interaction from at the molecular (aim 1), the cellular (aim 2), and organismal level and carry out drug discovery (aim 3).

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