Department of Biotechnology, Indian Institute of Technology Guwahati, Guwahati 781039, Assam, India.
Biochimie. 2011 May;93(5):962-8. doi: 10.1016/j.biochi.2011.02.006. Epub 2011 Feb 24.
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.
纤维状蛋白聚集体（称为淀粉样蛋白）在组织中的沉积是几种退行性疾病的根本原因。因此，鉴定可以预防或减少蛋白质聚集的化合物可以作为潜在的治疗靶点。在本研究中，我们已经证明四硫代硫酸钠钠对 pH 值为 2.0 的鸡卵清白溶菌酶（HEWL）淀粉样变形成的抑制作用。我们的研究表明，没有磺化作用，四硫代硫酸钠可以防止淀粉样纤维的进展。此外，它表明形成二硫键而不是蛋白质中疏水性表面的暴露在启动纤维形成过程中起着关键作用。还原剂β-巯基乙醇对纤维形成过程的抑制作用也证实了二硫键在启动 HEWL 淀粉样变形成中的作用。这些结果为理解指导淀粉样变形成的关键相互作用提供了重要信息，这可能有助于开发潜在的治疗方法。
