DNA REPAIR IN ALZHEIMER'S DISEASE

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。所列机构为 中心，不一定是研究者的机构。 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Ogg 1在AD发展中的作用。 我们的中心假设是，大脑中oxo-dG的积累导致神经元细胞死亡作为AD的病因因素，Ogg 1的增加可能会减轻这种损害。 我们已经制定了假设的基础上，我们的初步数据显示，oxo-dG和Ogg 1相应的增加，在兔子的大脑中喂养胆固醇，但没有在控制，一个模型，研究AD。 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）研究胆固醇诱导的类AD模型中主要的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Ogg 1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.