Vanillin Protects Dopaminergic Neurons against Inflammation-Mediated Cell Death by Inhibiting ERK1/2, P38 and the NF-κB Signaling Pathway.
Vanillin Protects Dopaminergic Neurons against Inflammation-Mediated Cell Death by Inhibiting ERK1/2, P38 and the NF-κB Signaling Pathway.
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香兰素通过抑制 ERK1/2、P38 和 NF-kappa B 信号通路保护多巴胺能神经元免受炎症介导的细胞死亡
DOI：
10.3390/ijms18020389
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发表时间：
2017-02-12
影响因子：
5.6
通讯作者：
Liu JX
中科院分区：
文献类型：
--
作者：
Yan X;Liu DF;Zhang XY;Liu D;Xu SY;Chen GX;Huang BX;Ren WZ;Wang W;Fu SP;Liu JX
神经炎症在帕金森病（PD）的发病机制中起着重要作用。激活后，小胶质细胞产生促炎介质，损害周围的神经元。因此，抑制小胶质细胞的活化可能是PD治疗的新途径。香草醛已被证明可以保护多巴胺能神经元，但其机制尚不清楚。在此，我们进一步研究了脂多糖（LPS）诱导的PD模型的潜在机制。在体内实验中，我们首先通过单侧黑质注射脂多糖（LPS）建立PD大鼠模型，然后研究香草醛在运动功能障碍、小胶质细胞活化和多巴胺能神经元变性中的作用。在体外实验中，在LPS孵育之前，用香草醛处理小鼠小胶质细胞BV-2细胞，然后分析炎症反应和相关信号通路。在体实验结果表明，香草醛可明显改善LPS所致的运动功能障碍，抑制多巴胺能神经元变性，抑制小胶质细胞过度激活。体外研究表明，香草醛通过调节ERK 1/2、p38和NF-κB信号通路，降低LPS诱导的诱导型一氧化氮（iNOS）、环氧合酶-2（考克斯-2）、IL-1β和IL-6的表达。总的来说，这些数据表明，香草醛具有通过抑制炎症活化来保护多巴胺能神经元的作用。
Neuroinflammation plays a very important role in the pathogenesis of Parkinson’s disease (PD). After activation, microglia produce pro-inflammatory mediators that damage surrounding neurons. Consequently, the inhibition of microglial activation might represent a new therapeutic approach of PD. Vanillin has been shown to protect dopaminergic neurons, but the mechanism is still unclear. Herein, we further study the underlying mechanisms in lipopolysaccharide (LPS)-induced PD models. In vivo, we firstly established rat models of PD by unilateral injection of LPS into substantia nigra (SN), and then examined the role of vanillin in motor dysfunction, microglial activation and degeneration of dopaminergic neurons. In vitro, murine microglial BV-2 cells were treated with vanillin prior to the incubation of LPS, and then the inflammatory responses and the related signaling pathways were analyzed. The in vivo results showed that vanillin markedly improved the motor dysfunction, suppressed degeneration of dopaminergic neurons and inhibited microglial over-activation induced by LPS intranigral injection. The in vitro studies demonstrated that vanillin reduces LPS-induced expression of inducible nitric oxide (iNOS), cyclooxygenase-2 (COX-2), IL-1β, and IL-6 through regulating ERK1/2, p38 and NF-κB signaling. Collectively, these data indicated that vanillin has a role in protecting dopaminergic neurons via inhibiting inflammatory activation.