Core C: Animals

项目摘要 目前，还没有预防或甚至减缓阿尔茨海默病（AD）进展的治疗方法， 这是最普遍的神经退行性疾病。动物核心（核心C）将提供正常和 转基因小鼠或大鼠，并将进行项目1，2和3中描述的实验。啮齿动物 表达与神经退行性疾病有关的人类蛋白质的模型被证明是发现 正常蛋白质的错误折叠形式，称为朊病毒，作为疾病的新原则。AD涉及两种朊病毒， 和Abeta。细胞测定允许测量培养物中的人tau和Abeta朊病毒，但转移人tau和Abeta朊病毒的细胞测定允许测量培养物中的人tau和Abeta朊病毒。 从人类到小鼠的疾病将提供必要的验证。将脑匀浆接种到特定的 啮齿动物大脑的区域和随后的疾病诊断需要非常熟练的动物 技术人员也通过评估临床体征和生物发光作为疾病的标志来评估疾病的发作。 疾病诱导的神经胶质增生的转基因模型专门为此目的（项目1和2）。稳定性 tau和Abeta朊病毒株或构象也将通过在小鼠中重复传代进行测试（项目2）。 异常高分辨率的结构（项目3）可以通过低温电子显微镜使用 核心C提供的材料。在Core C中执行的实验最终将提供模型进行测试 阻止疾病进展的疗法。

PROJECT SUMMARY At present, there is no treatment that prevents or even slows the progression of Alzheimer's disease (AD), which is the most prevalent neurodegenerative disorder. The Animal Core (Core C) will provide normal and genetically modified mice or rats and will conduct the experiments described in Projects 1, 2, and 3. Rodent models that express human proteins involved in neurodegenerative disease proved key in the discovery of misfolded forms of normal proteins, called prions, as new principles of disease. AD involves two prions, tau and Abeta. Cellular assays allow measurement of human tau and Abeta prions in culture, but transfer of disease from humans to mice will provide essential validation. Inoculation of brain homogenates into specific regions of the rodent brain and subsequent diagnosis of disease requires exceptionally skilled animal technicians who also assess disease onset by evaluating clinical signs and by bioluminescence as a marker of disease-induced gliosis in transgenic models specifically bred for this purpose (Projects 1 and 2). The stability of tau and Abeta prion strains or conformations also will be tested by repeated passage in mice (Project 2). Exceptionally high resolution structures (Project 3) can be determined by cryo-electron microscopy using material provided by Core C. The experiments executed in Core C ultimately will provide models to test therapies that halt disease progression.