首页> 美国卫生研究院文献>Proceedings of the National Academy of Sciences of the United States of America >Inhibition of amyloid-β aggregation and caspase-3 activation by the Ginkgo biloba extract EGb761
【2h】

Inhibition of amyloid-β aggregation and caspase-3 activation by the Ginkgo biloba extract EGb761

机译:银杏叶提取物EGB761对淀粉样β聚集和caspase-3活化的抑制作用

代理获取
本网站仅为用户提供外文OA文献查询和代理获取服务,本网站没有原文。下单后我们将采用程序或人工为您竭诚获取高质量的原文,但由于OA文献来源多样且变更频繁,仍可能出现获取不到、文献不完整或与标题不符等情况,如果获取不到我们将提供退款服务。请知悉。

摘要

Standardized extract from the leaves of the Ginkgo biloba tree, labeled EGb761, has been used in clinical trials for its beneficial effects on brain functions, particularly in connection with age-related dementias and Alzheimer's disease (AD). Substantial experimental evidence indicates that EGb761 protects against neuronal damage from a variety of insults, but its cellular and molecular mechanisms remain unknown. Using a neuroblastoma cell line stably expressing an AD-associated double mutation, we report that EGb761 inhibits formation of amyloid-β (Aβ) fibrils, which are the diagnostic, and possibly causative, feature of AD. The decreased Aβ fibrillogenesis in the presence of EGb761 was observed both in the conditioned medium of this Aβ-secreting cell line and in solution in vitro. In the cells, EGb761 significantly attenuated mitochondrion-initiated apoptosis and decreased the activity of caspase 3, a key enzyme in the apoptosis cell-signaling cascade. These results suggest that (i) neuronal damage in AD might be due to two factors: a direct Aβ toxicity and the apoptosis initiated by the mitochondria; and (ii) multiple cellular and molecular neuroprotective mechanisms, including attenuation of apoptosis and direct inhibition of Aβ aggregation, underlie the neuroprotective effects of EGb761.
机译:银杏树叶子的标准化提取物被标记为EGb761,由于其对脑功能的有益作用(特别是与年龄相关的痴呆症和阿尔茨海默氏病(AD)有关)已用于临床试验。大量的实验证据表明,EGB761可以防止各种损伤对神经元的损害,但其细胞和分子机制尚不清楚。我们使用稳定表达与AD相关的双突变的神经母细胞瘤细胞系,报道了EGb761抑制淀粉样β(Aβ)纤维的形成,这是AD的诊断性和可能的​​致病性。在该分泌Aβ的细胞系的条件培养基和体外溶液中均观察到在EGb761存在下Aβ原纤维形成的减少。在细胞中,EGb761显着减弱了线粒体引发的凋亡,并降低了胱天蛋白酶3的活性,胱天蛋白酶3是凋亡细胞信号级联反应中的关键酶。这些结果表明(i)AD中的神经元损伤可能是由于两个因素引起的:直接的Aβ毒性和由线粒体引发的凋亡。 (ii)EGb761的神经保护作用是多种细胞和分子神经保护机制,包括凋亡的减弱和Aβ聚集的直接抑制。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
代理获取

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