• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Cellular Physiology and Biochemistry >The Cholinergic Antagonist Gymnodimine Improves Aβ and Tau Neuropathology in an in Vitro Model of Alzheimer Disease
【24h】

The Cholinergic Antagonist Gymnodimine Improves Aβ and Tau Neuropathology in an in Vitro Model of Alzheimer Disease

机译：胆碱能拮抗剂Gymnodimine在阿尔茨海默氏病体外模型中改善Aβ和Tau神经病理学。

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Gymnodimine (GYM) is a marine phycotoxin with a macrocyclic imine structure, isolated from extracts of the dinoflagellate iKarenia selliformis/i known to act as a cholinergic antagonist with subtype selectivity. However, no data on the chronic effects of this compound has been reported so far. In this work, we evaluated the effect of long term exposure of cortical neurons to gymnodimine in the progress of Alzheimer disease (AD) pathology iin vitro/i. Treatment of cortical neurons with 50 nM gymnodimine decreased the intracellular amyloid beta (Aβ) accumulation and the levels of the hyperphosphorylated isoforms of tau protein recognized by AT8 and AT100 antibodies. These results are suggested to be mediated by the increase in the inactive isoform of the glycogen synthase kinase-3 (phospho GSK-3 Ser9), the decrease in the levels of the active isoform of the ERK1/2 kinase and the increase in acetylcholine (Ach) synthesis elicited by long term exposure of cortical neurons to the toxin. Moreover, gymnodimine decreased glutamate-induced neurotoxicity iin vitro/i. Altogether these results indicate that the marine phycotoxin gymnodimine may constitute a valuable tool for the development of drugs to treat neurodegenerative diseases.
机译：Gymnodimine（GYM）是一种具有大环亚胺结构的海洋植物毒素，是从狄诺鞭毛藻类植物卡累氏酵母的提取物中分离出来的，已知该提取物可作为胆碱能拮抗剂，具有亚型选择性。但是，到目前为止，尚未报道有关该化合物的慢性影响的数据。在这项工作中，我们评估了皮层神经元长期暴露于皮质神经元对阿尔茨海默氏病（AD）病理学进展的影响。用50 nM Gymnodimine处理皮质神经元可减少AT8和AT100抗体识别的细胞内淀粉样β（Aβ）积累和tau蛋白的超磷酸化同工型水平。这些结果被认为是由糖原合酶激酶3（磷酸GSK-3 Ser9）的非活性同工型增加，ERK1 / 2激酶的活性同工型水平降低和乙酰胆碱（ Ach）合成是由皮质神经元长期暴露于毒素引起的。此外，裸草胺在体外降低了谷氨酸诱导的神经毒性。总而言之，这些结果表明，海洋植物毒素裸子草胺可能构成开发用于治疗神经退行性疾病的药物的有价值的工具。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号