DNA REPAIR IN ALZHEIMER'S DISEASE

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 我们的长期目标是研究神经退行性变中DNA修复的机制。本研究的目的是确定Ogg1在阿尔茨海默病发生发展中的作用。我们的中心假设是，oxo-DG在大脑中的积累导致神经细胞死亡，这是AD的一个病因，Ogg1的增加可能会减轻这种损害。我们根据我们的初步数据提出了这一假说，该假说表明，在喂饲胆固醇的兔子的大脑中，oxo-DG和Ogg1的相应增加，但在对照组中没有，这是一种研究AD的模型。我们的研究将产生新的数据，可能表明这种疾病的新治疗靶点。目的1)确定胆固醇诱导的类AD模型的主要DNA损伤及其在神经细胞死亡中的作用。目的2)探讨DNA修复蛋白Ogg1在AD发病机制中的作用。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Our long-term goals are to investigate the mechanism of DNA repair in neurological degenerations. The objective of this research is to identify the role of Ogg1 in the development of AD. Our central hypothesis is that accumulation of oxo-dG in brains causes neuron cell death as an etiological factor for AD and that increase in Ogg1 may alleviate this damage. We have formulated the hypothesis based on our preliminary data showing oxo-dG and correspondent increase of Ogg1 in the brains of rabbits fed with cholesterol but not in the controls, a model for studying AD. Our research will result in novel data that may indicate novel therapeutic targets for this disease. Aim 1) To determine the main DNA lesion and its role in neural cell death in cholesterol induced AD like models. Aim 2) To investigate the roles of DNA repair protein Ogg1 in AD pathogenesis.