Department of General Biophysics, University of Lodz, Lodz, Poland.
Int J Biol Macromol. 2012 May 1;50(4):1138-43. doi: 10.1016/j.ijbiomac.2012.02.003. Epub 2012 Feb 13.
The aim of this work was to study the effect of phosphorus-containing dendrimers (generations G3 and G4) on the fibrillation of α-synuclein (ASN). The inhibition of fibril formation (filamentous and aggregates) is a potential therapeutic strategy for neurodegenerative disorders such as Parkinson's and other motor disorder neurodegenerative diseases. The interaction between phosphorus-containing dendrimers and ASN was studied by fluorescence spectroscopy. The decrease in the fluorescence intensity of intrisinic tyrosine was the most marked change in the fluorescence intensity observed upon addition of dendrimers. Furthermore, the effect of dendrimers on ASN fibril formation was studied using circular dichroism (CD) spectroscopy and CD studies were complemented by fluorescence assays using the dye thioflavin T (ThT). The results showed that phosphorus-containing dendrimers G3 and G4 inhibited fibril formation, when they were used in the ASN/dendrimer ratios 1:0.1 and 1:0.5. However, the higher concentrations of dendrimers did not show this effect.
这项工作的目的是研究含磷树枝状大分子(第 G3 代和 G4 代)对α-突触核蛋白(ASN)纤维化的影响。抑制纤维形成(丝状和聚集体)是治疗帕金森病和其他运动障碍神经退行性疾病等神经退行性疾病的潜在策略。通过荧光光谱研究了含磷树枝状大分子与 ASN 之间的相互作用。在加入树枝状大分子后,观察到的荧光强度最显著的变化是固有色氨酸的荧光强度降低。此外,还使用圆二色性(CD)光谱研究了树枝状大分子对 ASN 纤维形成的影响,并使用硫代黄素 T(ThT)染料的荧光测定法补充了 CD 研究。结果表明,当含磷树枝状大分子 G3 和 G4 以 ASN/树枝状大分子比 1:0.1 和 1:0.5 使用时,它们抑制纤维形成。然而,较高浓度的树枝状大分子则没有显示出这种效果。