SCI和EI收录∣中国化工学会会刊

中国化学工程学报 ›› 2023, Vol. 57 ›› Issue (5): 63-71.DOI: 10.1016/j.cjche.2022.09.013

• Full Length Article • 上一篇    下一篇

Proanthocyanidins prevent tau protein aggregation and disintegrate tau filaments

Huan-Huan Yin1, Yin-Lei Han1, Xiao Yan2, Yi-Xin Guan1   

  1. 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
  • 收稿日期:2022-06-23 修回日期:2022-08-31 出版日期:2023-05-28 发布日期:2023-07-08
  • 通讯作者: Xiao Yan,E-mail:xyan@mpi-cbg.de;Yi-Xin Guan,E-mail:guanyx@zju.edu.cn
  • 基金资助:
    This work was supported by the National Natural Science Foundation of China (21878262).

Proanthocyanidins prevent tau protein aggregation and disintegrate tau filaments

Huan-Huan Yin1, Yin-Lei Han1, Xiao Yan2, Yi-Xin Guan1   

  1. 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
  • Received:2022-06-23 Revised:2022-08-31 Online:2023-05-28 Published:2023-07-08
  • Contact: Xiao Yan,E-mail:xyan@mpi-cbg.de;Yi-Xin Guan,E-mail:guanyx@zju.edu.cn
  • Supported by:
    This work was 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 concentration-dependent 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)

Abstract: 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 concentration-dependent 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.

Key words: Protein, Aggregation, Disaggregation, Molecular simulation, Proanthocyanidins, Alzheimer’s disease (AD)