Naringenin Produces Neuroprotection Against LPS-Induced Dopamine Neurotoxicity via the Inhibition of Microglial NLRP3 Inflammasome Activation
Naringenin Produces Neuroprotection Against LPS-Induced Dopamine Neurotoxicity via the Inhibition of Microglial NLRP3 Inflammasome Activation
复制标题
柚皮素通过抑制小胶质细胞 NLRP3 炎性体激活，产生针对 LPS 诱导的多巴胺神经毒性的神经保护作用
DOI：
10.3389/fimmu.2019.00936
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发表时间：
2019-05-01
影响因子：
7.3
通讯作者：
Zhang, Feng
中科院分区：
文献类型：
--
作者：
Chen, Ce;Wei, Yi-Zheng;Zhang, Feng
背景资料：帕金森病（Parkinson's disease，PD）是第二大流行的中枢神经系统（CNS）退行性疾病，其特征在于中脑黑质中的多巴胺（DA）神经元的缓慢和进行性损失。小胶质细胞介导的神经炎症被认为是DA神经元丢失过程中的主要中枢事件。因此，抑制神经炎症可能是PD治疗的更可行策略。柚皮素（Naringenin，NAR）是一种存在于柑橘类和葡萄柚中的天然黄酮类化合物，具有一定的药理活性。最近的研究表明，NAR对几种神经系统疾病具有神经保护作用。然而，潜在的NAR产生的神经保护的机制并没有完全illuminated.Methods：在本研究中，大鼠黑质立体定向注射脂多糖（LPS）诱导的DA神经元的损失进行调查NAR介导的神经保护。结果：NAR对LPS诱导的DA神经元毒性有保护作用。此外，NAR抑制小胶质细胞炎性小体信号传导激活和随后的促炎因子释放。此外，NAR介导的DA神经保护作用依赖于对小胶质细胞NLRP 3炎性小体激活的抑制，这一点可以通过观察得到证明，即在小胶质细胞NLRP 3 siRNA处理后，NAR减少促炎因子的产生并进一步发挥DA神经保护作用以对抗LPS诱导的神经元损伤。这项研究表明，NAR靶向小胶质细胞NLRP 3炎性体，以保护DA神经元免受LPS诱导的神经毒性。这些结果提示NAR可能具有治疗PD的潜力。
Background: Parkinson's disease (PD) is the second most prevalent central nervous system (CNS) degenerative disease and characterized by slow and progressive loss of dopamine (DA) neurons in the midbrain substantia nigra. Microglia-mediated neuroinflammation has been considered as the major central event in the process of DA neuronal loss. Thus, inhibition of neuroinflammation could possess a more viable strategy for PD treatment. Naringenin (NAR), a natural flavanoid contained in citrus fruit and grapefruits, possesses amounts of pharmacological activities. Recent studies indicated that NAR produced neuroprotection against several neurological disorders. However, the mechanisms underlying NAR-generated neuroprotection are not fully illuminated.Methods: In the present study, rat nigral stereotaxic injection of lipopolysaccharide (LPS)-induced DA neuronal loss was performed to investigate NAR-mediated neuroprotection. In addition, BV-2 and MN9D cell lines were applied to explore the underlying mechanisms.Results: NAR protected DA neurons against LPS-induced neurotoxicity. Also, NAR suppressed microglial nod-like receptor protein 3 (NLRP3) inflammasome signaling activation and the subsequent pro-inflammatory factors release. In addition, NAR-mediated DA neuroprotection was dependent on the inhibition of microglial NLRP3 inflammasome activation, as evidenced by the observations that NAR-reduced pro-inflammatory factors production and further NAR-exerted DA neuroprotection against LPS-induced neuronal damage was not discerned after microglial NLRP3 siRNA treatment.Conclusions: This study demonstrated that NAR targeted microglial NLRP3 inflammasome to protect DA neurons against LPS-induced neurotoxicity. These findings suggest NAR might hold a promising therapeutic potential for PD.