Notoginsenoside R1-Induced Neuronal Repair in Models of Alzheimer Disease Is Associated With an Alteration in Neuronal Hyperexcitability, Which Is Regulated by Nav.
Notoginsenoside R1-Induced Neuronal Repair in Models of Alzheimer Disease Is Associated With an Alteration in Neuronal Hyperexcitability, Which Is Regulated by Nav.
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三七皂苷 R1 在阿尔茨海默病模型中诱导的神经元修复与神经元过度兴奋性的改变有关，而神经元过度兴奋性受 Nav 调节
DOI：
10.3389/fncel.2020.00280
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发表时间：
2020
影响因子：
5.3
通讯作者：
Wang XY
中科院分区：
文献类型：
--
作者：
Hu T;Li S;Liang WQ;Li SS;Lu MN;Chen B;Zhang L;Mao R;Ding WH;Gao WW;Chen SW;XiYang YB;Zhang J;Wang XY
阿尔茨海默病的特点是进行性认知缺陷，可能与神经网络异常的高兴奋性有关。三七皂苷R1 （Notoginsenoside R1，简称R1）是三七的主要活性成分，在多种疾病引起的脑损伤中显示出良好的神经元可塑性变化和神经保护作用，但其机制尚不清楚。在本研究中，我们旨在探讨R1在AD小鼠模型中可能诱导的神经保护作用及其机制。R1通过改变电压门控钠通道（Nav）成员的数量和/或分布，显著改善了淀粉样前体蛋白/早老素-1小鼠的学习和记忆功能，并纠正了神经元的高兴奋性。此外，我们还确定了R1是否参与了a β-42损伤细胞神经元兴奋性的调节。我们的研究结果表明，R1通过增加细胞活力来拯救a β1-42诱导的损伤神经元。r1诱导的神经元高兴奋性减轻可能与Navβ2切割减少有关，这部分逆转了Nav1.1α的异常分布。这些结果表明，R1在a β1-42诱导的神经元损伤和高兴奋性的恢复中发挥了重要作用，并受Nav蛋白的调控。因此，R1可能是治疗AD的有希望的候选药物。
Alzheimer disease is characterized by a progressive cognitive deficit and may be associated with an aberrant hyperexcitability of the neuronal network. Notoginsenoside R1 (R1), a major activity ingredient from Panax notoginseng, has demonstrated favorable changes in neuronal plasticity and induced neuroprotective effects in brain injuries, resulting from various disorders, however, the underlying mechanisms are still not well understood. In the present study, we aimed to explore the possible neuroprotective effects induced by R1 in a mouse model of AD and the mechanisms underlying these effects. Treatment with R1 significantly improved learning and memory functions and redressed neuronal hyperexcitability in amyloid precursor protein/presenilin-1 mice by altering the numbers and/or distribution of the members of voltage-gated sodium channels (Nav). Moreover, we determined whether R1 contributed to the regulation of neuronal excitability in Aβ-42–injured cells. Results of our study demonstrated that treatment with R1 rescued Aβ1-42–induced injured neurons by increasing cell viability. R1-induced alleviation in neuronal hyperexcitability might be associated with reduced Navβ2 cleavage, which partially reversed the abnormal distribution of Nav1.1α. These results suggested that R1 played a vital role in the recovery of Aβ1-42–induced neuronal injury and hyperexcitability, which is regulated by Nav proteins. Therefore, R1 may be a promising candidate in the treatment of AD.
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影响因子：
4.4
作者：
Liu, Juanfang;Yan, Xiaodong;Zhao, Gang
通讯作者：
Zhao, Gang
DOI：
10.1073/pnas.1206171109
发表时间：
2012-05-29
影响因子：
11.1
作者：
Busche, Marc Aurel;Chen, Xiaowei;Konnerth, Arthur
通讯作者：
Konnerth, Arthur
影响因子：
4.6
作者：
Ciccone, Roselia;Franco, Cristina;Pannaccione, Anna
通讯作者：
Pannaccione, Anna
影响因子：
4.8
作者：
Chen, Feng;Eckman, Elizabeth A.;Eckman, Christopher B.
通讯作者：
Eckman, Christopher B.
影响因子：
1.7
作者：
Huang, Jinlan;Wu, Dengpan;Zhong, Zhenguo
通讯作者：
Zhong, Zhenguo