DNA repair dysfunction in neurodegeneration

神经退行性疾病中的 DNA 修复功能障碍

• 批准号: 7964023
• 负责人: Vilhelm Bohr
• 金额: $ 25.82万
• 依托单位: NATIONAL INSTITUTE ON AGING
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7964023
• 关键词: Age; Aging; Biochemical; Biological Assay; Brain; Cellular Assay; DNA; DNA Damage; DNA Repair; Functional disorder; Glutamates; Human; Individual; Learning; Mus; Nerve Degeneration; Neurons; Neurotransmitters; Nucleotide Excision Repair; Oxidative Stress; Pathway interactions; Process; Rattus; Synapses; UV induced DNA damage; attenuation; mouse model; neurotransmission; novel; oxidative DNA damage; repaired; theories; ultraviolet damage

We have studied DNA repair in individual primary rat neurons. These neurons repair many kinds of DNA damage, and it is particularly novel that they repair UV induced DNA damage. This is important because UV damage to DNA is removed by the DNA repair process called nucleotide excision repair, which is generally thought to be deficient in the CNS. We also find attenuation of oxidative DNA damage repair in differentiating neurons and we find that the DNA repair in the synaptic region is quite robust after oxidative stress. Furthermore, there seems to be a connection between neurotransmission and DNA repair because the addition of neurotransmitters to neurons incraeses the DNA damage and repair. Specifically, Glutamate, the most abundant neurotransmitter directly stimulates DNA repair in a pathway that we are currently exploring. This raises the possibility that a connection exists between DNA repair and learning.

我们研究了单个大鼠初级神经元的DNA修复。这些神经元可以修复多种DNA损伤，其中修复紫外线诱导的DNA损伤是一项特别新颖的研究。这一点很重要，因为紫外线对DNA的损伤是通过DNA修复过程（称为核苷酸切除修复）来消除的，而这种修复过程通常被认为是中枢神经系统的缺陷。我们还发现分化神经元氧化DNA损伤修复的衰减，我们发现突触区域的DNA修复在氧化应激后相当强劲。此外，神经传递和DNA修复之间似乎存在联系，因为向神经元添加神经递质会增加DNA损伤和修复。具体来说，谷氨酸，最丰富的神经递质直接刺激DNA修复的途径，我们目前正在探索。这提出了DNA修复和学习之间存在联系的可能性。