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Abstract：
Oxidative stress is a common feature of neurodegenerative diseases. Different natural compounds mediate neuroprotective effects by activating the Nrf2 antioxidant response. Some isothiocyanates are Nrf2 activators, including Moringin (MOR). In this study, the transcriptional profile of differentiated NSC-34 motor neurons was evaluated after treatment for 48 h and 96 h with concentrations of 0.5, 5, and 10 µM of a new MOR formulation obtained with α-cyclodextrin (α-CD). All the concentrations increased gene expression and cytoplasmic protein levels of Nrf2 at 96 h. However, the highest dose also increased nuclear Nrf2 levels at 96 h. Then, Nrf2 interactors were selected using STRING, and common biological process (BP) terms between the groups were evaluated. α-CD/MOR was able to modulate BP related to responses to oxidative stress, proteostasis, and autophagy. Specifically, the treatment with 10 µM of α-CD/MOR for 96 h induced genes involved in glutathione synthesis and proteasome subunits and reduced the expression of genes related to endoplasmic reticulum stress. Moreover, this group showed the lowest levels of the apoptotic markers Bax, cleaved caspase 9, and cleaved caspase 3. These results indicate the beneficial effects of prolonged α-CD/MOR supplementation that are mediated, at least in part, by Nrf2 activation. Then, α-CD/MOR could be a valuable treatment against neurodegenerative diseases, in particular motor neuron degeneration.
摘要：
氧化应激是神经退行性疾病的共同特征。不同的天然化合物通过激活Nrf2抗氧化反应来介导神经保护作用。一些异硫氰酸酯是Nrf2活化剂，包括辣素（MOR）。在这项研究中,用α-环糊精(α-CD)获得的新型MOR制剂浓度为0.5,5和10µM,分别处理48h和96h后,评估分化的NSC-34运动神经元的转录谱.所有浓度在96小时时都增加了Nrf2的基因表达和胞质蛋白水平。最高剂量也增加了96小时的核Nrf2水平。然后，使用STRING选择Nrf2交互体，并对各组间的共同生物过程(BP)术语进行评价。α-CD/MOR能够调节与氧化应激反应相关的BP，proteostasis,和自噬。具体来说,用10µMα-CD/MOR处理96h可诱导参与谷胱甘肽合成和蛋白酶体亚基的基因，并降低与内质网应激相关的基因表达。此外，该组显示的凋亡标志物Bax水平最低，裂解的半胱天冬酶9和裂解的半胱天冬酶3。这些结果表明，延长α-CD/MOR补充的有益作用是介导的，至少在某种程度上,通过Nrf2激活。然后，α-CD/MOR可能是一种有价值的治疗神经退行性疾病，特别是运动神经元变性。
