In vivo Studies of Ginkgo biloba Neuroprotection

阿尔茨海默病(AD)的发病率在美国稳步上升，这是我们的平均水平 寿命延长了。因此，预防或降低这种疾病的发生率的手段对 医学研究。银杏叶标准化提取物(EGb761)已用于治疗 某些与衰老和阿尔茨海默病相关的大脑功能障碍和痴呆。确凿的证据表明 EGb 761具有神经保护作用。然而，提取物的作用机制很差。 明白了。我们之前由美国国立卫生研究院资助的研究为 银杏叶提取物761体外抗淀粉样蛋白聚集和抗细胞凋亡作用 作为潜在的重要神经保护作用机制。 这个跨学科项目的目标是加深我们对神经保护的理解。 银杏叶提取物761的体内作用机制。我们将继续检验这一假设，即神经保护作用 银杏叶提取物761是通过抑制Aβ齐聚、抗氧化性能和增强血管紧张素转换酶而获得的。 生物体的内源性应激反应。我们将使用转基因线虫模型与 建立阿尔茨海默病转基因小鼠模型，研究Aβ聚集、氧化和毒性之间的可能联系。 本项目的具体目标是：1)将银杏叶提取物761对Aβ聚集的影响与 Aβ沉积的荧光染色毒性及Aβ致麻痹的行为学分析 在表达人Aβ基因的线虫中；2)确定银杏叶蛋白单一组分的活性 761通过对可诱导转基因C. 3)研究EGB 761对野生型和小鼠基因转录的影响 4)检测银杏叶提取物761对人类认知功能的影响 _通过在AD转基因小鼠模型中测试海马区依赖的空间学习来进行配对。 前期成果和初步数据证明了该项目的可行性。更好地理解 EGB 761的神经保护机制将对理解潜在的 神经退行性变过程和设计针对神经退行性变的治疗策略 精神错乱。

The incidence of Alzheimer's disease (AD) has steadily increased in the United States as our average lifespan has lengthened. Thus, the means to prevent or reduce the rate of this disorder is a high priority for medical research. A standardized extract of Ginkgo biloba leaves (EGb 761) has been used for treatment of certain cerebral dysfunctions and dementias associated with aging and AD. Substantial evidence indicates that EGb 761 has neuroprotective effects. The action mechanisms of the extract are, however, poorly understood. Our previous studies funded by the National Institutes of Health provided evidence for the anti-amyloid beta (A beta) aggergation and anti-apoptotic properties of EGb 761 in vitro, which hold promise as potentially important neuroprotective mechanisms of action. The goal of this interdisciplinary project is to further our understanding of the neuroprotective mechanisms of EGb 761 in vivo. We will continue to test the hypothesis that the neuroprotective effect of EGb 761 is achieved by inhibition of A beta oligomerization, antioxidative properties and augmentation of an organism's endogenous stress-response. We will use transgenic C. elegans models in conjunction with a transgenic mouse model of AD to study possible links between A beta aggregation, oxidation and toxicity. The specific aims of the present project are: 1) to correlate effects of EGb 761 on A beta aggregation and toxicity through fluorescence staining of A beta deposits and behavioral analysis of A beta-induced paralysis in the transgenic C. elegans expressing human A beta; 2) to define activities of single constituents of EGb 761 against A beta-induced oxidation through kinetic study of protein carbonyls in an inducible transgenic C. elegans; 3) to implicate changes in gene transcription profile induced by EGb 761 in the wild type and the transgenic C. elegans, using DNA microarray method, 4) to determine effects of EGb 761 on cognitive _mpairment through testing hippocampus-dependent spatial learning in a transgenic mouse model of AD. Previous results and preliminary data show the feasibility of this project. A better understanding of the 'mechanisms of EGb 761 neuroprotection will be important for understanding of the underlying neurodegenerative processes and for designing therapeutic strategies that target neurodegenerative disorders.