Ellagic Acid Protects Dopamine Neurons via Inhibition of NLRP3 Inflammasome Activation in Microglia.
Ellagic Acid Protects Dopamine Neurons via Inhibition of NLRP3 Inflammasome Activation in Microglia.
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鞣花酸通过抑制小胶质细胞中 NLRP3 炎症小体的激活来保护多巴胺神经元
DOI：
10.1155/2020/2963540
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发表时间：
2020
影响因子：
--
通讯作者：
Zhang F
中科院分区：
文献类型：
--
作者：
He XM;Zhou YZ;Sheng S;Li JJ;Wang GQ;Zhang F
神经炎症在帕金森病（PD）的病理过程中起着至关重要的作用。 Nod样受体蛋白3（NLRP3）炎症小体在小胶质细胞中高度定位，参与神经炎症过程。 NLRP3 炎性体的激活已被证实有助于 PD 的进展。因此，抑制NLRP3炎性体激活可能是PD治疗的重要突破点。鞣花酸 (EA) 是一种天然多酚，广泛存在于软果、坚果和其他植物组织中，具有抗炎、抗氧化和神经保护特性。然而，EA 介导的抗炎和神经保护机制尚未完全阐明。在本研究中，建立了脂多糖（LPS）诱导的大鼠多巴胺（DA）神经元损伤模型，以确定电针对 DA 神经元保护的作用。此外，使用DA神经元MN9D细胞系和小胶质细胞BV-2细胞系来探讨EA介导的神经保护是否通过NLRP3依赖性机制。结果表明，EA 改善了 LPS 诱导的大鼠黑质 DA 神经元损失。此外，如以下观察结果所证明，小胶质细胞 NLRP3 炎性体信号传导激活的抑制参与了 EA 产生的神经保护作用。首先，EA 减少了小胶质细胞中 NLRP3 炎性体信号传导的激活以及随后促炎细胞因子的排泄。其次，小胶质细胞 NLRP3 siRNA 治疗后并未显示出 EA 介导的抗神经炎症和针对 LPS 诱导的神经毒性的进一步 DA 神经保护作用。总之，本研究证明 EA 通过抑制小胶质细胞 NLRP3 炎性体激活，对保护 DA 神经元免受 LPS 诱导的神经毒性具有深远的影响。
Neuroinflammation plays a crucial role in the pathological process of Parkinson's disease (PD). Nod-like receptor protein 3 (NLRP3) inflammasome was highly located in microglia and involved in the process of neuroinflammation. Activation of the NLRP3 inflammasome has been confirmed to contribute to the progression of PD. Thus, inhibition of NLRP3 inflammasome activation could be an important breakthrough point on PD therapy. Ellagic acid (EA) is a natural polyphenol that has been widely found in soft fruits, nuts, and other plant tissues with anti-inflammatory, antioxidant, and neuroprotective properties. However, the mechanisms underlying EA-mediated anti-inflammation and neuroprotection have not been fully elucidated. In this study, a lipopolysaccharide- (LPS-) induced rat dopamine (DA) neuronal damage model was performed to determine the effects of EA on the protection of DA neurons. In addition, the DA neuronal MN9D cell line and microglial BV-2 cell line were employed to explore whether EA-mediated neuroprotection was through an NLRP3-dependent mechanism. Results indicated that EA ameliorated LPS-induced DA neuronal loss in the rat substantia nigra. Further, inhibition of microglial NLRP3 inflammasome signaling activation was involved in EA-generated neuroprotection, as evidenced by the following observations. First, EA reduced NLRP3 inflammasome signaling activation in microglia and subsequent proinflammatory cytokines' excretion. Second, EA-mediated antineuroinflammation and further DA neuroprotection from LPS-induced neurotoxicity were not shown upon microglial NLRP3 siRNA treatment. In conclusion, this study demonstrated that EA has a profound effect on protecting DA neurons against LPS-induced neurotoxicity via the suppression of microglial NLRP3 inflammasome activation.
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DOI：
10.1002/mds.27037
发表时间：
2017-07
期刊：
Movement disorders : official journal of the Movement Disorder Society
影响因子：
--
作者：
Collier TJ;Kanaan NM;Kordower JH
通讯作者：
Kordower JH
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
64.8
作者：
Shao, Wei;Zhang, Shu-zhen;Zhou, Jia-wei
通讯作者：
Zhou, Jia-wei
影响因子：
--
作者：
Firdaus F;Zafeer MF;Anis E;Ahmad M;Afzal M
通讯作者：
Afzal M
星形胶质细胞上的 Kir6.1/K-ATP 通道通过促进线粒体自噬预防帕金森病 MPTP 小鼠模型中的多巴胺能神经变性
影响因子：
15.1
作者：
Hu, Zhao-Li;Sun, Ting;Hu, Gang
通讯作者：
Hu, Gang