Kanapathipillai Mathumai, Lentzen Georg, Sierks Michael, Park Chan Beum
Department of Chemical and Materials Engineering, Arizona State University, Tempe, AZ 85287, USA.
FEBS Lett. 2005 Aug 29;579(21):4775-80. doi: 10.1016/j.febslet.2005.07.057.
beta-Amyloid peptide (Abeta) is the major constituent of senile plaques, the key pathological feature of Alzheimer's disease. Abeta is physiologically produced as a soluble form, but aggregation of Abeta monomers into oligomers/fibrils causes neurotoxic change of the peptide. In nature, many microorganisms accumulate small molecule chaperones (SMCs) under stressful conditions to prevent the misfolding/denaturation of proteins and to maintain their stability. Hence, it is conceivable that SMCs such as ectoine and hydroxyectoine could be potential inhibitors against the aggregate formation of Alzheimer's Abeta, which has not been studied to date. The current work shows the effectiveness of ectoine and hydroxyectoine on the inhibition of Abeta42 aggregation and toxicity to human neuroblastoma cells. The characterization tools used for this study include thioflavin-T induced fluorescence, atomic force microscopy and cell viability assay. Considering that ectoine and hydroxyectoine are not toxic to cellular environment even at concentrations as high as 100 mM, the results may suggest a basis for the development of ectoines as potential inhibitors associated with neurodegenerative diseases.
β-淀粉样肽（Aβ）是老年斑的主要成分，而老年斑是阿尔茨海默病的关键病理特征。Aβ在生理状态下以可溶形式产生，但Aβ单体聚集成寡聚体/原纤维会导致该肽发生神经毒性变化。在自然界中，许多微生物在应激条件下会积累小分子伴侣（SMC），以防止蛋白质错误折叠/变性并维持其稳定性。因此，可以想象诸如四氢嘧啶和羟基四氢嘧啶之类的小分子伴侣可能是阿尔茨海默病Aβ聚集形成的潜在抑制剂，而迄今为止尚未对此进行研究。当前的研究表明了四氢嘧啶和羟基四氢嘧啶在抑制Aβ42聚集以及对人神经母细胞瘤细胞毒性方面的有效性。本研究中使用的表征工具包括硫黄素-T诱导荧光、原子力显微镜和细胞活力测定。鉴于四氢嘧啶和羟基四氢嘧啶即使在高达100 mM的浓度下对细胞环境也无毒，这些结果可能为开发作为与神经退行性疾病相关的潜在抑制剂的四氢嘧啶类物质提供了依据。
