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<p>Aggregation and deposition of amyloid-β protein (Aβ42) in extracellular spaces are key neuropathological features of Alzheimer’s disease (AD). Extracellular Aβ42 aggregates not only impair the function of the extracellular matrix but also directly damage brain cells through binding interactions. Chemically, tea polyphenols are amphiphilic, similar to the Aβ42 molecule. This study found that catechin (CA) and epigallocatechin gallate (EGCG) effectively bound to Aβ42 monomers (Aβ42M) and oligomers (Aβ42O), preventing Aβ42 aggregation; in contrast, EGCG also showed some binding to protofibrils (Aβ42P) and fibrils (Aβ42F), slightly inhibiting their development. In the presence of Aβ42M and Aβ42 aggregates in vitro, CA and EGCG demonstrated considerable protective effects on neural and vascular endothelial cells. These effects corresponded with the ability of CA and EGCG (particularly CA) to preserve Aβ42M’s targeting and binding to these cells, while they (especially EGCG) blocked or inhibited Aβ42O’s targeting and binding. Molecular docking revealed that both CA and EGCG effectively maintained the active conformation of Aβ42M; in contrast, EGCG also effectively rendered Aβ42O units inactive, primarily by disrupting and covering the hydrophobic clusters. Furthermore, CA and EGCG improved the AD brain microenvironment, including reducing Aβ42 plaque burden and supporting brain cell populations. In conclusion, CA and EGCG inhibited the structure, bioactivity, and cell-targeting ability of Aβ42 aggregates; however, they protected these aspects of Aβ42M. These findings are essential for understanding the neuroprotective mechanisms of plant polyphenols.</p>

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Neuroprotective Effects of Catechins by Differentially Affecting the Binding of Beta-amyloid and Its Aggregates to the Target Cells

  • 期刊论文

  • 发表日期：

    2025年4月2日

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  • He Li,
  • Changxin Zheng,
  • Zhenxing Wang,
  • Kai Wen,
  • Yingjiu Zhang

摘要

Aggregation and deposition of amyloid-β protein (Aβ42) in extracellular spaces are key neuropathological features of Alzheimer’s disease (AD). Extracellular Aβ42 aggregates not only impair the function of the extracellular matrix but also directly damage brain cells through binding interactions. Chemically, tea polyphenols are amphiphilic, similar to the Aβ42 molecule. This study found that catechin (CA) and epigallocatechin gallate (EGCG) effectively bound to Aβ42 monomers (Aβ42M) and oligomers (Aβ42O), preventing Aβ42 aggregation; in contrast, EGCG also showed some binding to protofibrils (Aβ42P) and fibrils (Aβ42F), slightly inhibiting their development. In the presence of Aβ42M and Aβ42 aggregates in vitro, CA and EGCG demonstrated considerable protective effects on neural and vascular endothelial cells. These effects corresponded with the ability of CA and EGCG (particularly CA) to preserve Aβ42M’s targeting and binding to these cells, while they (especially EGCG) blocked or inhibited Aβ42O’s targeting and binding. Molecular docking revealed that both CA and EGCG effectively maintained the active conformation of Aβ42M; in contrast, EGCG also effectively rendered Aβ42O units inactive, primarily by disrupting and covering the hydrophobic clusters. Furthermore, CA and EGCG improved the AD brain microenvironment, including reducing Aβ42 plaque burden and supporting brain cell populations. In conclusion, CA and EGCG inhibited the structure, bioactivity, and cell-targeting ability of Aβ42 aggregates; however, they protected these aspects of Aβ42M. These findings are essential for understanding the neuroprotective mechanisms of plant polyphenols.