Hematoxylin Inhibits Amyloid β-Protein Fibrillation and Alleviates Amyloid-Induced Cytotoxicity
2016
Accumulation and aggregation of amyloid β-protein (Aβ) play an important role in the pathogenesis of Alzheimer’s disease. There has been increased interest in finding new anti-amyloidogenic compounds to inhibit Aβ aggregation. Herein, thioflavin T fluorescent assay and transmission electron microscopy results showed that hematoxylin, a natural organic molecule extracted from Caesalpinia sappan, was a powerful inhibitor of Aβ42 fibrillogenesis. Circular dichroism studies revealed hematoxylin reduced the β-sheet content of Aβ42 and made it assemble into antiparallel arrangement, which induced Aβ42 to form off-pathway aggregates. As a result, hematoxylin greatly alleviated Aβ42-induced cytotoxicity. Molecular dynamics simulations revealed the detailed interactions between hematoxylin and Aβ42. Four binding sites of hematoxylin on Aβ42 hexamer were identified, including the N-terminal region, S8GY10 region, turn region, and C-terminal region. Notably, abundant hydroxyl groups made hematoxylin prefer to intera...
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