Mechanisms of Ginkgo biloba Neuropotection

描述（由申请人提供）：神经退行性疾病影响 随着寿命的增长，我们人口中的比例越来越大。因此，在本发明中， 预防或降低这些疾病发生率的方法是一个高度优先事项 用于医学研究本项目的目标是了解 银杏叶提取物EGb761的神经保护机制。EGb761已成为 最受欢迎的制剂之一，特别是用于预防和 治疗与衰老相关的原发性神经变性痴呆， 老年痴呆症大量的实验证据支持神经保护 EGb761的性质，但其作用的实际机制还不清楚 未知我们将检验标准化提取物EGb 761具有 神经保护的多个作用部位，至少部分， 通过抗氧化、抗淀粉样蛋白生成和 抗凋亡机制。本项目的具体目标是：1. 评价EGb761的抗氧化和抗淀粉样蛋白生成机制，2.识别 EGb761的细胞存活途径。培养的海马脑片和神经元 细胞将被用作氧化应激和神经毒性的模型。 最先进的分子和细胞技术以及药理学 抑制剂和活化剂的应用将被用来确定潜在的 EGb761神经保护作用的途径。所有必需的方法都在 放置在PI的实验室和合作者的实验室中。结果 这些实验可应用于动物模型和人体研究。更好 了解EGb 761的神经保护机制将是重要的 不仅是为了设计合理的“基于机制”的战略， 年龄相关的神经退行性疾病，但也为基本了解 潜在的神经退化过程本身。

DESCRIPTION (provided by applicant): Neurodegenerative disorders are affecting larger and larger proportions of our population as lifespan increases. Thus, the means to prevent or reduce the rate of these disorders is a high priority for medical research. The goal of this project is to gain understanding of the neuroprotective mechanisms of Ginkgo biloba extract EGb761. EGb761 has become one of the most popular preparations, especially for the prevention and treatment of primary neurodegenerative dementias associated with aging and Alzheimer's disease. Substantial experimental evidence supports neuroprotective properties of EGb761, but the actual mechanisms of its action(s) is yet unknown. We will test the hypothesis that the standardized extract EGb761 has multiple sites of action for neuroprotection, which is, at least in part, achieved by interaction of antioxidative, anti-amyloidogenic, and anti-apoptotic mechanisms. The specific aims of the present project are: 1. Evaluate antioxidative and anti-amyloidogenic mechanisms of EGb761, 2. Identify cell survival pathways of EGb761. Cultured hippocampal slices and neuronal cells will be used as models of oxidative stress and neurotoxicity. State-of-the art molecular and cellular techniques and pharmacological application of inhibitors and activators will be used to define the potential pathways of EGb761 neuroprotection. All of the required methodologies are in place in the PI's laboratory and in those of the collaborators. Results from these experiments can be applied to animal models and human studies. Better understanding of the mechanisms of neuroprotection by EGb761 will be important not only for design of rational "mechanism-based" strategies that target age-related neurodegenerative disorders, but also for basic understanding of the underlying neurodegenerative processes themselves.