State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China.
Shanghai Key Laboratory of Signaling and Disease Research, Collaborative Innovation Center for Brain Science, School of Life Sciences and Technology, Tongji University, Shanghai, China.
Front Immunol. 2020 Feb 27;11:162. doi: 10.3389/fimmu.2020.00162. eCollection 2020.
Neuroinflammation induced by overactivated glia cells is believed to be a major hallmark of Alzheimer's disease (AD) and a hopeful target against AD. A rhamnoside PL201 was previously reported to promote neurogenesis and ameliorate AD, and in this study, we revealed that PL201 also significantly reduced accumulation of the activated microglia and proinflammatory cytokines in APP/PS1 mice. , PL201 consistently suppressed the microglia induction of proinflammatory cytokines after stimulation with lipopolysaccharides and Aβ42. Further mechanistic studies demonstrated that PL201 considerably enhanced the expression level and the nuclear translocation of Nrf2, a key regulator of neuroinflammation. Moreover, PL201 effectively stimulated Nrf2 signaling cascade, including upregulation of HO-1 and downregulation of NF-κB pathway. Thus, our findings indicated the anti-neuroinflammatory effect by PL201 and suggested that PL201 or the like, with multiple functions such as neurogenesis, mitochondria maintenance, and anti-neuroinflammation, could be a promising candidate in AD treatment.
过度激活的神经胶质细胞引起的神经炎症被认为是阿尔茨海默病（AD）的一个主要标志，也是对抗 AD 的一个有希望的靶点。先前有报道称鼠李糖苷 PL201 可促进神经发生并改善 AD，在本研究中，我们发现 PL201 还可显著减少 APP/PS1 小鼠中活化的小胶质细胞和促炎细胞因子的积累。PL201 还能持续抑制脂多糖和 Aβ42 刺激后小胶质细胞中促炎细胞因子的诱导。进一步的机制研究表明，PL201 可显著增强核转录因子 Nrf2 的表达水平和核转位，Nrf2 是神经炎症的关键调节因子。此外，PL201 还能有效激活 Nrf2 信号级联反应，包括 HO-1 的上调和 NF-κB 通路的下调。因此，我们的研究结果表明 PL201 具有抗神经炎症作用，并提示 PL201 或类似物具有神经发生、线粒体维持和抗神经炎症等多种功能，可能成为 AD 治疗的一个有前途的候选药物。
