Inhibition of amyloid-beta aggregation and caspase-3 activation by the Ginkgo biloba extract EGb761.
Inhibition of amyloid-beta aggregation and caspase-3 activation by the Ginkgo biloba extract EGb761.
复制标题
DOI：
--
复制
发表时间：
2002
影响因子：
11.1
通讯作者：
Yuan Luo;J. Smith;V. Paramasivam;Adam Burdick;K. Curry;Justin P Buford;I. Khan;William J. Netzer-William-J.
中科院分区：
文献类型：
--
作者：
Yuan Luo;J. Smith;V. Paramasivam;Adam Burdick;K. Curry;Justin P Buford;I. Khan;William J. Netzer-William-J.
银杏叶的标准化提取物（标记为 EGb761）因其对大脑功能的有益影响而被用于临床试验，特别是与年龄相关的痴呆症和阿尔茨海默氏病 (AD)。大量实验证据表明 EGb761 可以保护神经元免受各种损伤，但其细胞和分子机制仍不清楚。使用稳定表达 AD 相关双突变的神经母细胞瘤细胞系，我们报告 EGb761 抑制淀粉样蛋白-β (Abeta) 原纤维的形成，这是 AD 的诊断特征，也可能是其致病特征。在该 Abeta 分泌细胞系的条件培养基和体外溶液中都观察到 EGb761 存在下 Abeta 原纤维生成减少。在细胞中，EGb761 显着减弱线粒体引发的细胞凋亡，并降低凋亡细胞信号级联中的关键酶 caspase 3 的活性。这些结果表明（i）AD 中的神经元损伤可能是由于两个因素造成的：直接的 Abeta 毒性和线粒体引发的细胞凋亡； (ii) 多种细胞和分子神经保护机制，包括减弱细胞凋亡和直接抑制 Abeta 聚集，是 EGb761 神经保护作用的基础。
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-beta (Abeta) fibrils, which are the diagnostic, and possibly causative, feature of AD. The decreased Abeta fibrillogenesis in the presence of EGb761 was observed both in the conditioned medium of this Abeta-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 Abeta toxicity and the apoptosis initiated by the mitochondria; and (ii) multiple cellular and molecular neuroprotective mechanisms, including attenuation of apoptosis and direct inhibition of Abeta aggregation, underlie the neuroprotective effects of EGb761.