CALCIUM REGULATION IN BRAIN AGING AND ALZHEIMERS DISEASE

这是一份申请竞争性续展计划的申请书 专注于钙调节在脑老化中的作用的项目 和阿尔茨海默病以及神经元基础的基本过程 脆弱性。在之前的一段时间里，项目中的调查人员 项目能够阐明钙离子的一些关键变化 衰老动物脑细胞的调节和模型的调节 神经变性/阿尔茨海默病。还获得了新的证据 钙调节的这种变化可能与 神经退行性变过程。此外，方案项目调查人员 发现了新的线索，并对几个假设进行了测试 年龄相关性钙调节失调的可能病因基础。 在接下来的时期内，建议进行全面的 脑老化与钙调节的研究进展 阿尔茨海默氏症，使用先进的钙成像技术， 电生理学和分子生物学。计划项目(PGP)将 由五个项目和一个行政核心组成。这些项目将 检验钙代谢失调初始原因的几个假说 包括类固醇激素的作用(它有特定的靶点 在脑细胞中)，功能和大脑能量的基因表达改变 新陈代谢。钙离子失调的特定神经元部位将 被检测对象包括膜离子通道、内质网、 线粒体、细胞骨架和细胞内信号通路。在……里面 此外，相关研究将直接在尸检大脑上进行。 AD患者和对照组的组织。 PGP将调查人员聚集在一起，对 钙调节和神经毒性的机制，以及 先进技术。这些调查人员将共享重叠的模型 并在相关主题上广泛协作，从而确保强有力的 交叉受精和多学科结合是关键 问题正在调查中。

This is an application for a competitive continuation of a program project that focuses on the role of Calcium Regulation in Brain Aging and Alzheimer's Disease and on basic processes that underlie neuronal vulnerability. During the prior period, investigators in the program project were able to elucidate a number of key changes in calcium regulation in brain cells of aging animals and in models of neurodegeneration/Alzheimer's disease. New evidence was also obtained that such changes in calcium regulation may be directly relevant to neurodegenerative processes. In addition, program project investigators uncovered new leads and performed tests of several hypotheses on the possible causal bases of age-related calcium dysregulation. During the next period, it is proposed to pursue a comprehensive approach to the study of calcium regulation in brain aging and Alzheimer's disease, using advanced technologies for calcium imaging, electrophysiology and molecular biology. The Program Project (PGP) will consist of five projects and one administrative core. The projects will test several hypotheses of the initial causes of calcium dysregulation including the role of steroid hormones (which have specific target sites in brain cells), altered gene expression of function, and brain energy metabolism. Specific neuronal sites of calcium dysregulation that will be examined include membrane ion channels, endoplasmic reticulum, mitochondria, the cytoskeleton and intracellular signaling pathways. In addition, related studies will be conducted directly on autopsy brain tissues from AD and control subjects. The PGP brings together investigators with a natural interest in the mechanisms of calcium regulation and neurotoxicity, and skills in advanced technologies. These investigators will share overlapping models and collaborate extensively on related subjects, thereby ensuring strong cross-fertilization and multi-disciplinary approaches to the key questions under investigation.