Neuroprotective Studies of Evodiamine in an Okadaic Acid-Induced Neurotoxicity.
Neuroprotective Studies of Evodiamine in an Okadaic Acid-Induced Neurotoxicity.
复制标题
DOI：
10.3390/ijms22105347
复制
发表时间：
2021-05-19
影响因子：
5.6
通讯作者：
Yang CR
中科院分区：
文献类型：
--
作者：
Chou CH;Yang CR
背景：阿尔茨海默病（Alzheimer's disease，AD）是最常见的神经退行性疾病，主要表现为进行性记忆丧失和认知功能下降。然而，目前尚无有效的治疗方法，这是一个亟待解决的问题。吴茱萸碱是吴茱萸的主要活性成分之一，在缺血和AD小鼠模型中具有改善血脑屏障（BBB）通透性和改善认知功能障碍的作用。然而，吴茱萸碱是否能抑制tau蛋白病仍不清楚。本研究旨在检查吴茱萸碱是否改善AD模型中的tau磷酸化和认知缺陷。方法：用蛋白磷酸酶2A抑制剂冈田酸（OA）诱导tau蛋白磷酸化，模拟神经元AD样模型。Western blotting检测蛋白表达，流式细胞仪检测细胞凋亡。在OA诱导的小鼠模型中使用水迷宫、被动回避试验和磁共振成像测定来评估空间记忆/认知，并通过免疫组织化学进一步评估脑切片。结果如下：结果表明，吴茱萸碱显著降低磷酸化tau蛋白的表达，并进一步减少tau蛋白聚集和神经元细胞死亡响应OA处理。这种抑制作用是通过抑制糖原合成酶激酶3β、细胞周期蛋白依赖性激酶5和丝裂原活化蛋白激酶途径实现的。在体内的结果表明，吴茱萸碱治疗改善小鼠的学习和记忆障碍，而小鼠大脑的蛋白质印迹和免疫组织化学分析也证实了吴茱萸碱的神经保护作用。结论：吴茱萸碱可减轻tau蛋白聚集的神经毒性，具有神经保护作用。我们的研究结果表明，吴茱萸碱具有治疗AD的治疗潜力。
Background: Alzheimer’s disease (AD) is the most common neurodegenerative disease, and it manifests as progressive memory loss and cognitive decline. However, there are no effective therapies for AD, which is an urgent problem to solve. Evodiamine, one of the main bioactive ingredients of Evodia rutaecarpa, has been reported to ameliorate blood–brain barrier (BBB) permeability and improve cognitive impairment in ischemia and AD mouse models. However, whether evodiamine alleviates tauopathy remains unclear. This study aimed to examine whether evodiamine ameliorates tau phosphorylation and cognitive deficits in AD models. Methods: A protein phosphatase 2A inhibitor, okadaic acid (OA), was used to induce tau phosphorylation to mimic AD-like models in neuronal cells. Protein expression and cell apoptosis were detected using Western blotting and flow cytometry, respectively. Spatial memory/cognition was assessed using water maze, passive avoidance tests, and magnetic resonance imaging assay in OA-induced mice models, and brain slices were evaluated further by immunohistochemistry. Results: The results showed that evodiamine significantly reduced the expression of phosphor-tau, and further decreased tau aggregation and neuronal cell death in response to OA treatment. This inhibition was found to be via the inhibition of glycogen synthase kinase 3β, cyclin-dependent kinase 5, and mitogen-activated protein kinase pathways. In vivo results indicated that evodiamine treatment ameliorated learning and memory impairments in mice, whereas Western blotting and immunohistochemical analysis of the mouse brain also confirmed the neuroprotective effects of evodiamine. Conclusions: Evodiamine can decrease the neurotoxicity of tau aggregation and exhibit a neuroprotective effect. Our results demonstrate that evodiamine has a therapeutic potential for AD treatment.
登录
查看更多内容
影响因子：
4.3
作者：
Kimura T;Sharma G;Ishiguro K;Hisanaga SI
通讯作者：
Hisanaga SI
影响因子：
2.9
作者：
Zhang Z;Simpkins JW
通讯作者：
Simpkins JW
影响因子：
2.7
作者：
Kobayashi, Y;Nakano, Y;Kamiya, T
通讯作者：
Kamiya, T
影响因子：
4.2
作者：
Engel, Tobias;Lucas, Jose J.;Hernandez, Felix
通讯作者：
Hernandez, Felix
影响因子：
3.2
作者：
Das, Tushar Kanti;Jana, Piyali;Hamid, Mas R. W. Abdul
通讯作者：
Hamid, Mas R. W. Abdul