Effect of sodium tetrathionate on amyloid fibril: Insight into the role of disulfide bond in amyloid progression.

Tissue deposition of fibrillar protein aggregates called amyloid is the root cause of several degenerative diseases. Thus identification of compounds which can prevent or reduce protein aggregation can serve as a potential therapeutic target. In the present study we have shown inhibitory effect of sodium tetrathionate toward Hen egg white lysozyme (HEWL) amyloidogenesis at pH 2.0. Our study reveals that without sulfonation, sodium tetrathionate prevents amyloid fibril progression. Moreover, it shows that formation of disulfide bonds rather than exposure of hydrophobic surface in protein plays a critical role in initiating fibrillation process. Inhibitory effect of reducing agent β-mercaptoethanol toward fibrillation process also confirms the involvement of disulfide bond in initiating HEWL amyloidogenesis. These results provide important information toward understanding key interactions that guide amyloidogenesis, which may facilitate development of potential therapeutics.