Istituto di Biomedicina ed Immunologia Molecolare (IBIM), CNR, via Ugo La Malfa, 153, 90146, Palermo, Italy.
Free Radic Res. 2009;43(11):1133-45. doi: 10.1080/10715760903214454.
Oxidative stress and dysfunctional mitochondria are among the earliest events in AD, triggering neurodegeneration. The use of natural antioxidants could be a neuroprotective strategy for blocking cell death. Here, the antioxidant action of ferulic acid (FA) on different paths leading to degeneration of recombinant beta-amyloid peptide (rAbeta42) treated cells was investigated. Further, to improve its delivery, a novel drug delivery system (DDS) was used. Solid lipid nanoparticles (SLNs), empty or containing ferulic acid (FA-SNL), were developed as DDS. The resulting particles had small colloidal size and highly negative surface charge in water. Using neuroblastoma cells and rAbeta42 oligomers, it was demonstrated that free and SLNs-loaded FA recover cell viability. FA treatment, in particular if loaded into SLNs, decreased ROS generation, restored mitochondrial membrane potential (Deltapsi(m)) and reduced cytochrome c release and intrinsic pathway apoptosis activation. Further, FA modulated the expression of Peroxiredoxin, an anti-oxidative protein, and attenuated phosphorylation of ERK1/2 activated by Abeta oligomers.
氧化应激和功能失调的线粒体是 AD 中最早发生的事件之一，引发神经退行性变。使用天然抗氧化剂可能是阻止细胞死亡的神经保护策略。在这里，研究了阿魏酸 (FA) 对导致重组β-淀粉样肽 (rAbeta42) 处理细胞变性的不同途径的抗氧化作用。此外，为了改善其传递，使用了一种新的药物传递系统 (DDS)。制备了固体脂质纳米粒 (SLNs)，空的或含有阿魏酸 (FA-SLN) 的 SLNs。所得颗粒在水中具有小的胶体粒径和高度负的表面电荷。使用神经母细胞瘤细胞和 rAbeta42 低聚物，证明游离和 SLNs 负载的 FA 可恢复细胞活力。FA 处理，特别是负载到 SLNs 中，可减少 ROS 的产生，恢复线粒体膜电位 (Deltapsi(m))，并减少细胞色素 c 释放和内在途径凋亡的激活。此外，FA 调节了抗氧化蛋白 Peroxiredoxin 的表达，并减弱了 Abeta 低聚物激活的 ERK1/2 的磷酸化。
