Reduced Nicotinamide Adenine Dinucleotide Phosphate Inhibits MPTP-Induced Neuroinflammation and Neurotoxicity
Reduced Nicotinamide Adenine Dinucleotide Phosphate Inhibits MPTP-Induced Neuroinflammation and Neurotoxicity
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还原型烟酰胺腺嘌呤二核苷酸磷酸抑制 MPTP 诱导的神经炎症和神经毒性
DOI：
10.1016/j.neuroscience.2018.08.032
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发表时间：
2018-11
期刊：
影响因子：
3.3
通讯作者：
Qin Zheng-Hong
中科院分区：
文献类型：
--
作者：
Zhou Ying;Wu Junchao;Sheng Rui;Li Mei;Wang Yan;Han Rong;Han Feng;Chen Zhong;Qin Zheng-Hong
目前普遍认为氧化应激和神经炎症与帕金森病（PD）的发病机制有关。还原型烟酰胺腺嘌呤二核苷酸磷酸（NADPH）已被证明对氧化应激具有有效的神经保护作用。在本研究中，我们研究了NADPH是否可以通过抑制1-甲基-4-苯基-1，2，3，6-四氢吡啶（MPTP）诱导的胶质细胞介导的神经炎症来提供神经保护，这是一种有助于PD发病机制的机制。目前的数据表明，MPTP/MPP+除了诱导核因子-κB（NF-κB）的核转位和p38 MAPK的磷酸化外，还增加了黑质（SNpc）中活性氧（ROS）、活化的胶质细胞和炎性体蛋白的水平。这些反应被抑制补充外源性NADPH。此外，NADPH在体外研究中有效地减少MPP+诱导的小胶质细胞BV-2细胞中ROS、p38磷酸化和炎性蛋白COX 2（COX 2）的过度产生。类似地，p38 MAPK抑制剂SB 203580抑制MPP+诱导的p38磷酸化和COX 2蛋白水平的上调。将神经元细胞与MPP+致敏的BV-2细胞共培养，增加了肿瘤坏死因子-α（TNF-α）的水平，并诱导神经元细胞的细胞死亡。TNF-α中和抗体和NADPH可减弱上述作用。NADPH减少MPTP诱导的运动功能障碍和多巴胺能（DA）细胞的损失。因此，本研究表明，NADPH保护DA神经元，通过抑制氧化应激和胶质介导的神经炎症在体外和体内，从而表明PD和其他神经退行性疾病的临床应用的潜力。
It is generally believed that oxidative stress and neuroinflammation are implicated in the pathogenesis of Parkinson’s disease (PD). Reduced nicotinamide adenine dinucleotide phosphate (NADPH) has been demonstrated to have potent neuroprotective effects against oxidative stress. In the present research, we investigated if NADPH could offer neuroprotection by inhibiting glia-mediated neuroinflammation induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a mechanism contributing to PD pathogenesis. The current data demonstrated that MPTP/MPP+increased levels of reactive oxygen species (ROS), activated glial cells, and inflammasome proteins in the substantia nigra (SNpc), in addition to inducing the nuclear translocation of nuclear factor-κB (NF-κB) and phosphorylation of p38 MAPK. These responses were inhibited by supplementation of exogenous NADPH. Moreover, NADPH effectively decreased MPP+-induced excessive production of ROS, p38 phosphorylation and inflammatory protein of Cyclooxygenase2 (COX2) in cultured microglial BV-2 cells in vitro studies. Similarly, the p38 MAPK inhibitor SB203580 suppressed the upregulation of MPP+-induced p38 phosphorylation and COX2 protein levels. Co-culture of neuronal cells with MPP+-primed BV-2 cells increased the levels of tumor necrosis factor-alpha (TNF-α) and induced cell death of neuronal cells. These effects were diminished by TNF-α neutralizing antibody and NADPH. NADPH reduced motor dysfunction and the loss of dopaminergic (DA) cells induced by MPTP. Therefore, the present study demonstrates that NADPH protects DA neurons by inhibiting oxidative stress and glia-mediated neuroinflammation both in vitro and in vivo, thus suggesting a potential of clinical application for PD and other neurodegenerative diseases.
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DOI：
10.1201/b12952-20
发表时间：
2021-04
期刊：
The Lancet
影响因子：
--
作者：
B. Bloem;M. Okun;C. Klein
通讯作者：
B. Bloem;M. Okun;C. Klein
影响因子：
7.4
作者：
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通讯作者：
Smeyne, Richard Jay
影响因子：
5.2
作者：
Figueiredo-Pereira ME;Corwin C;Babich J
通讯作者：
Babich J
影响因子：
4.8
作者：
Rai SN;Birla H;Singh SS;Zahra W;Patil RR;Jadhav JP;Gedda MR;Singh SP
通讯作者：
Singh SP
MicroRNA-7靶向Nod样受体蛋白3炎症小体调节帕金森病发病机制中的神经炎症
影响因子：
15.1
作者：
Zhou Y;Lu M;Du RH;Qiao C;Jiang CY;Zhang KZ;Ding JH;Hu G
通讯作者：
Hu G