4.7 Article

Hematoxylin modulates tau-RD protein fibrillization and ameliorates Alzheimer's disease-like symptoms in a yeast model

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DOI: 10.1016/j.ijbiomac.2023.126140

Keywords

Alzheimer's disease; Tau protein; Hematoxylin; Aggregation; Disaggregation; Molecular dynamics simulation

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This study discovered that hematoxylin has dual functionality in inhibiting tau protein fibrillogenesis and remodeling pre-formed fibrils. It also reduces the accumulation of tau aggregates. Hematoxylin interacts with tau protein through various forces and reduces cytotoxicity. Therefore, it may be a promising candidate for the treatment of Alzheimer's disease.
Alzheimer's disease (AD) is one of the most serious neurodegenerative diseases with no effective treatment options available. The formation of insoluble amyloid fibrils of the hyperphosphorylated tau protein is intimately associated with AD, hence the tau protein has been a key target for AD drug development. In this work, hematoxylin was discovered as a dual functional compound, that is, acting in the inhibition of repeat domain of tau (tau-RD) protein fibrillogenesis and remodeling of pre-formed tau-RD fibrils in vitro. Meanwhile, hematoxylin was able to reduce the accumulation of tau-RD aggregates in Saccharomyces cerevisiae. Experimental and computational studies indicated that hematoxylin directly interacts with tau-RD protein through hydrophobic forces, hydrogen bonds, pi-cation interactions, and pi-pi stackings. In addition, cellular viability assays showed that hematoxylin greatly reduced cytotoxicity induced by tau-RD aggregates. In summary, hematoxylin might be a promising candidate for further development as a potential therapeutic drug for AD patients.

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