Faculty of Biomedical Engineering, Amirkabir University of Technology, Tehran, Iran.
Department of Biomedical Engineering, Meybod University, Meybod, Iran.
Biotechnol Appl Biochem. 2019 Jul;66(4):537-544. doi: 10.1002/bab.1751. Epub 2019 Jul 8.
Amyloid fibrils, including β-amyloid (Aβ) fibrils, are protein aggregates that form under certain conditions, associated with neurodegeneration that interfere with neural synaptic transmission resulting in some neural disorders, such as Alzheimer's disease. The aim of this study is to inhibit amyloidogenesis by using preparatory polymeric nanomicelles as therapeutic agents and also as nanocarriers for curcumin to target Aβ fibrils through the glycation method of bovine serum albumin (BSA) in the presence of phosphate-buffered saline. Polymeric nanomicelles were prepared from phosphatidylethanolamine-distearoyl methoxypolyethylene glycol conjugates in the presence and absence of curcumin and then the morphological and structural characteristics of the nanomicelles were characterized in detail. Following the preparation of unloaded and curcumin-loaded nanomicelles with the desired size and properties, their effects on BSA glycation/fibrillation process were investigated. The samples were analyzed by thioflavin T (ThT) fluorescence and advanced glycation end (AGE) products autofluorescence measurements. The results showed that ThT fluorescence related to the formation of β-sheets and AGE autofluorescence (associated with AGE production) decreased in the presence of curcumin-loaded nanomicelles more than other samples. In conclusion, the promising effect of curcumin-loaded nanomicelles on inhibition of amyloidogenesis through glycation process due to curcumin release and thus their ability to prevent the formation and accumulation of amyloid fibrils and so to suppress the Alzheimer's disease progression has been proven and can go for further investigations.
淀粉样纤维,包括β-淀粉样蛋白(Aβ)纤维,是在特定条件下形成的蛋白质聚集物,与神经退行性变有关,干扰神经突触传递,导致一些神经紊乱,如阿尔茨海默病。本研究的目的是通过使用预备性聚合纳米胶束作为治疗剂,并通过牛血清白蛋白(BSA)的糖化方法将姜黄素作为纳米载体靶向 Aβ 纤维,来抑制淀粉样生成,在磷酸盐缓冲盐水存在下。在存在和不存在姜黄素的情况下,从磷脂酰乙醇胺-二硬脂酰基甲氧基聚乙二醇缀合物中制备聚合纳米胶束,然后详细表征纳米胶束的形态和结构特征。在制备具有所需尺寸和性能的未加载和姜黄素加载纳米胶束后,研究了它们对 BSA 糖基化/纤维形成过程的影响。通过硫黄素 T(ThT)荧光和晚期糖基化终产物(AGE)产物自体荧光测量分析样品。结果表明,在姜黄素加载纳米胶束存在下,与β-折叠形成相关的 ThT 荧光和 AGE 自体荧光(与 AGE 产生相关)降低,比其他样品更明显。总之,已经证明了姜黄素加载纳米胶束通过糖化过程抑制淀粉样生成的有希望的效果,这归因于姜黄素的释放,从而能够防止淀粉样纤维的形成和积累,从而抑制阿尔茨海默病的进展,可以进一步研究。