Sulforaphane protects against rotenone-induced neurotoxicity in vivo: Involvement of the mTOR, Nrf2, and autophagy pathways.
Sulforaphane protects against rotenone-induced neurotoxicity in vivo: Involvement of the mTOR, Nrf2, and autophagy pathways.
复制标题
DOI：
10.1038/srep32206
复制
发表时间：
2016-08-24
影响因子：
4.6
通讯作者：
Cao P
中科院分区：
文献类型：
--
作者：
Zhou Q;Chen B;Wang X;Wu L;Yang Y;Cheng X;Hu Z;Cai X;Yang J;Sun X;Lu W;Yan H;Chen J;Ye J;Shen J;Cao P
萝卜硫素是一种在十字花科蔬菜中发现的天然化合物，已被证明对几种神经系统疾病具有神经保护作用。在这项研究中，我们试图研究萝卜硫素在体内帕金森病（PD）模型中的潜在保护作用和相关分子机制，基于鱼藤酮介导的神经毒性。结果表明，萝卜硫素可以抑制鱼藤素引起的运动活性缺乏和多巴胺能神经元的丧失。此外，萝卜硫素处理抑制鱼藤酮诱导的活性氧产生、丙二醛（MDA）积累，并导致脑内总谷胱甘肽和还原谷胱甘肽（GSH）：氧化谷胱甘肽（GSSG）水平升高。Western blot分析显示，萝卜硫素增加了核因子（红细胞衍生2）样2 （Nrf2）、血红素加氧酶-1 （HO-1）和NAD(P)H醌氧化还原酶（NQO1）的表达，后两者均为抗氧化酶。此外，萝卜硫素处理显著减弱鱼藤酮抑制的mtor介导的p70S6K和4E-BP1信号通路，以及神经元凋亡。此外，通过LC3-II检测，萝卜硫素挽救了鱼藤素抑制的自噬。总的来说，这些发现表明萝卜硫素发挥神经保护作用，包括nrf2依赖性氧化应激的减少，mtor依赖性神经元凋亡的抑制，以及正常自噬的恢复。萝卜硫素是一种具有神经保护作用的有前景的化合物，可能在预防帕金森病中发挥重要作用。
Sulforaphane, a naturally occurring compound found in cruciferous vegetables, has been shown to be neuroprotective in several neurological disorders. In this study, we sought to investigate the potential protective effects and associated molecular mechanisms of sulforaphane in an in vivo Parkinson’s disease (PD) model, based on rotenone-mediated neurotoxicity. Our results showed that sulforaphane inhibited rotenone-induced locomotor activity deficiency and dopaminergic neuronal loss. Additionally, sulforaphane treatment inhibited the rotenone-induced reactive oxygen species production, malondialdehyde (MDA) accumulation, and resulted in an increased level of total glutathione and reduced glutathione (GSH): oxidized glutathione (GSSG) in the brain. Western blot analysis illustrated that sulforaphane increased the expression of nuclear factor (erythroid-derived 2)-like 2 (Nrf2), heme oxygenase-1 (HO-1), and NAD(P)H quinone oxidoreductase (NQO1), the latter two of which are anti-oxidative enzymes. Moreover, sulforaphane treatment significantly attenuated rotenone-inhibited mTOR-mediated p70S6K and 4E-BP1 signalling pathway, as well as neuronal apoptosis. In addition, sulforaphane rescued rotenone-inhibited autophagy, as detected by LC3-II. Collectively, these findings demonstrated that sulforaphane exert neuroprotective effect involving Nrf2-dependent reductions in oxidative stress, mTOR-dependent inhibition of neuronal apoptosis, and the restoration of normal autophagy. Sulforaphane appears to be a promising compound with neuroprotective properties that may play an important role in preventing PD.