Proanthocyanidins prevent tau protein aggregation and disintegrate tau filaments  

作　　者：Huan-Huan Yin Yin-Lei Han Xiao Yan Yi-Xin Guan 

机构地区：[1]College of Chemical and Biological Engineering,Zhejiang University,Hangzhou 310027,China [2]Max Planck Institute of Molecular Cell Biology and Genetics,Dresden 01307,Germany

出　　处：《Chinese Journal of Chemical Engineering》2023年第5期63-71,共9页中国化学工程学报（英文版）

基　　金：supported by the National Natural Science Foundation of China (21878262)。

摘　　要：Occurrence of neurofibrillary tangles of the tau protein is a hallmark of tau-related neurodegenerative diseases, i.e. Alzheimer's disease(AD) and frontotemporal dementia. The pathological mechanism underlying AD remains poorly understood, and effective treatments are still unavailable to mitigate the disease.Inhibiting of tau aggregation and disrupting the existing fibrils are key targets in drug discovery towards preventing or curing AD. In this study, grape seed proanthocyanidins(GSPs) was found to effectively inhibit the repeat domain of tau(tau-RD) aggregation and disaggregate tau-RD fibrils in a concentrationdependent manner by inhibiting β-sheet formation of tau-RD. In cells, GSPs relieved cytotoxicity induced by tau-RD aggregates. Molecular dynamics simulations indicated that strong hydrogen bonding,hydrophobic interaction and π-π stacking between GSPs and tau-RD protein were major reasons why GSPs had high inhibitory activity on tau-RD fibrillogenesis. These results provide preliminary data to develop GSPs into medicines, foodstuffs or nutritional supplements for AD patients, suggesting that GSPs could be a candidate molecule in the drug design for AD therapeutics.

关 键 词：Protein AGGREGATION DISAGGREGATION Molecular simulation PROANTHOCYANIDINS Alzheimer’s disease(AD) 

分 类 号：R749.16[医药卫生—神经病学与精神病学]