Autophagy is Involved in Neuroprotective Effect of Alpha7 Nicotinic Acetylcholine Receptor on Ischemic Stroke.
Autophagy is Involved in Neuroprotective Effect of Alpha7 Nicotinic Acetylcholine Receptor on Ischemic Stroke.
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自噬参与 Alpha7 烟碱乙酰胆碱受体对缺血性中风的神经保护作用
DOI：
10.3389/fphar.2021.676589
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发表时间：
2021
影响因子：
5.6
通讯作者：
Liu C
中科院分区：
文献类型：
--
作者：
Xu ZQ;Zhang JJ;Kong N;Zhang GY;Ke P;Han T;Su DF;Liu C
α7烟碱乙酰胆碱受体（α 7 nAChR）属于半胱氨酸环阳离子配体门控通道超家族，由均一的α7亚基组成。虽然本实验室发现激活α 7 nAChR可以减轻缺血性脑卒中，但其机制尚不清楚。在此，我们探讨自噬是否参与了缺血性脑卒中中α 7 nAChR介导的神经保护作用。分别采用短暂性大脑中动脉闭塞（tMCAO）和氧糖剥夺（OGD/R）暴露于缺血性卒中的体内和体外模型。在体内研究中，神经功能缺损评分和梗死体积用于评价tMCAO的结局。Western blot检测自噬相关蛋白，mRFP-GFP-LC 3慢病毒检测自噬通量。tMCAO后24 h，α 7 nAChR基因敲除小鼠的神经功能较野生型小鼠差，梗死体积较大。PNU 282987是一种α 7 nAChR激动剂，可保护OGD/R诱导的神经元损伤，增强自噬，并促进自噬通量。然而，PNU 282987的有益作用被3-甲基腺嘌呤（3-MA）（一种自噬抑制剂）消除。此外，我们发现PNU 282987处理可以在体外研究中激活AMPK-mTOR-p70 S6 K信号通路，而AMPK抑制剂化合物C减弱了该作用。我们的研究结果表明，通过激活α 7 nAChR对神经元存活的有益作用与增强的自噬有关，并且AMPK-mTOR-p70 S6 K信号通路参与了α 7 nAChR激活介导的神经保护作用。
The α7 nicotinic acetylcholine receptor (α7nAChR) belongs to the superfamily of cys loop cationic ligand-gated channels, which consists of homogeneous α7 subunits. Although our lab found that activation of α7nAChR could alleviate ischemic stroke, the mechanism is still unknown. Herein, we explored whether autophagy is involved in the neuroprotective effect mediated by α7nAChR in ischemic stroke. Transient middle cerebral artery occlusion (tMCAO) and oxygen and glucose deprivation (OGD/R) exposure were applied to in vivo and in vitro models of ischemic stroke, respectively. Neurological deficit score and infarct volume were used to evaluate outcomes of tMCAO in the in vivo study. Autophagy-related proteins were detected by Western blot, and autophagy flux was detected by using tandem fluorescent mRFP-GFP-LC3 lentivirus. At 24 h after tMCAO, α7nAChR knockout mice showed worse neurological function and larger infarct volume than wild-type mice. PNU282987, an α7nAChR agonist, protected against OGD/R-induced neuronal injury, enhanced autophagy, and promoted autophagy flux. However, the beneficial effects of PNU282987 were eliminated by 3-methyladenine (3-MA), an autophagy inhibitor. Moreover, we found that PNU282987 treatment could activate the AMPK-mTOR-p70S6K signaling pathway in the in vitro study, while the effect was attenuated by compound C, an AMPK inhibitor. Our results demonstrated that the beneficial effect on neuronal survival via activation of α7nAChR was associated with enhanced autophagy, and the AMPK-mTOR-p70S6K signaling pathway was involved in α7nAChR activation–mediated neuroprotection.
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影响因子：
4.7
作者：
Han Z;Li L;Wang L;Degos V;Maze M;Su H
通讯作者：
Su H
DOI：
10.1073/pnas.1009485107
发表时间：
2010-08-10
影响因子：
11.1
作者：
Lipinski, Marta M.;Zheng, Bin;Yuan, Junying
通讯作者：
Yuan, Junying
影响因子：
--
作者：
Jiang, Mei;Wang, Hairong;Li, Longxuan
通讯作者：
Li, Longxuan
ALDH2 通过清除 4-HNE 预防中风
影响因子：
44.1
作者：
通讯作者：
--
在MPTP小鼠模型中，α7烟碱乙酰胆碱受体介导的对多巴胺能神经元丧失的神经保护通过抑制星形胶质细胞激活。
影响因子：
9.3
作者：
Liu Y;Hu J;Wu J;Zhu C;Hui Y;Han Y;Huang Z;Ellsworth K;Fan W
通讯作者：
Fan W