Mechanisms of Ginkgo biloba Neuropotection

描述(申请人提供)：神经退行性疾病影响 随着寿命的延长，我们的人口比例越来越大。因此， 预防或降低这些疾病发生率的手段是当务之急 用于医学研究。这个项目的目标是了解 银杏叶提取物EGb761的神经保护机制。EGb761已经变成了 最受欢迎的制剂之一，尤其是预防和预防 原发性神经退行性痴呆的治疗与衰老和 阿尔茨海默氏症。大量实验证据支持神经保护 EGb761的性质，但其实际作用机制(S)尚不清楚 未知。我们将检验标准提取物EGb761具有 神经保护的多个作用部位，这至少是部分， 通过抗氧化、抗淀粉样变性和 抗细胞凋亡机制。本项目的具体目标是：1. 评估EGb761的抗氧化和抗淀粉样变性的机制，2.鉴定 EGb761的细胞存活途径。培养的海马片与神经元 细胞将被用作氧化应激和神经毒性的模型。 最新的分子和细胞技术及药理学 应用抑制剂和激活剂来确定潜力 EGb761的神经保护途径。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。结果来自 这些实验可以应用于动物模型和人体研究。更好 了解EGb761的神经保护机制具有重要意义。 不仅是为了设计合理的“基于机制的”战略，也就是 年龄相关的神经退行性疾病，也是为了基本了解 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.