Physics Department, Università degli Studi di Milano, Milano, Italy; INSTM Consortium, Milano, Italy.
Biotechnology and Biosciences Department, Università degli Studi di Milano-Bicocca, Milano, Italy.
Int J Biol Macromol. 2018 May;111:1100-1105. doi: 10.1016/j.ijbiomac.2018.01.112. Epub 2018 Jan 31.
Protein aggregation underlies many human diseases characterized by the deposition of normally soluble proteins in both fibrillar and amorphous aggregates. Here, Atomic Force Microscopy (AFM) has been applied to investigate the ability to inhibit hen egg white lysozyme (HEWL) fibrillogenesis by hydroxytyrosol (HT), one of the main phenolic components of olive oil. In this framework, HEWL is a useful and well-studied model protein whose amyloid-like fibril formation can be induced under experimental conditions where HT is more stable. HEWL fibrils, obtained at pH 1.6 and at 65 °C, exhibited a height of about 3 nm and a fibril length on average of about 3 μm. The presence of HT reduced the HEWL fibril number and length with respect to the control sample. Interestingly, also dopamine, a compound with a chemical structure similar to HT, decreased both the fibril number and the fibril length. AFM experimental data were supported by Thioflavin T assay and Fourier transform infrared spectroscopy. Our results show that HT is an effective inhibitor of HEWL aggregation, thus suggesting possible future applications of this natural compound for potential prevention or treatment of amyloid diseases, or as a lead molecular structure for the design of improved modulators.
蛋白质聚集是许多人类疾病的基础，这些疾病的特征是正常可溶性蛋白质在纤维状和无定形聚集物中沉积。在这里，原子力显微镜（AFM）已被应用于研究羟基酪醇（HT）抑制鸡卵清溶菌酶（HEWL）纤维化的能力，HT 是橄榄油的主要酚类成分之一。在这种情况下，HEWL 是一种有用且研究充分的模型蛋白，其类似淀粉样的纤维形成可以在 HT 更稳定的实验条件下诱导。在 pH 1.6 和 65°C 下获得的 HEWL 纤维表现出约 3nm 的高度和平均约 3μm 的纤维长度。与对照样品相比，HT 的存在减少了 HEWL 纤维的数量和长度。有趣的是，与 HT 化学结构相似的多巴胺也降低了纤维的数量和长度。AFM 实验数据得到了硫黄素 T 测定和傅里叶变换红外光谱的支持。我们的结果表明，HT 是 HEWL 聚集的有效抑制剂，因此表明这种天然化合物可能在预防或治疗淀粉样疾病方面具有潜在的应用，或者作为设计改良调节剂的先导分子结构。
