MITOCHONDRIAL DNA DELETIONS

最近的研究结果表明，脑线粒体DNA(MtDNA)缺失 这些缺失随着年龄的增长而增加，而且这些缺失在不同地区是不同的。A 4977 研究发现，脑线粒体DNA碱基缺失随年龄增长而增加 神经节、黑质和额叶皮质。相比之下，mtDNA很少 在小脑中发现缺失。此外，7463碱基对线粒体DNA水平 研究发现，这些脑区的缺失随着年龄的增长而增加。在……里面 此外，大脑线粒体dna密码子331的点突变似乎是升高的。 阿尔茨海默氏症。有人建议测量大脑线粒体dna的水平。 额叶皮质4977、7463和密码子331点突变， 年龄匹配的大脑中的内侧颞叶皮质、壳核和小脑 非痴呆对照受试者和阿尔茨海默病患者。 初步结果表明，这些mtdna缺失是可以测量到的。 使用定量聚合酶链式反应方法。现建议： 比较正常和阿尔茨海默病患者大脑的数量和 线粒体DNA缺失的区域特异性。我们将尝试 相关的病理发现(例如斑块计数、神经原纤维 缠结计数)与mtDNA缺失的范围和分布有关。一个 线粒体DNA缺失的可能来源是由以下因素引起的氧化应激 发炎。多种炎性物质刺激培养的人 星形细胞瘤细胞产生白介素1(IL-1)和 白介素6(IL-6)。IL-6促进异常神经元分化和 细胞凋亡论。IL-6和IL-1均促进阿尔茨海默病的合成 疾病β-淀粉样前体蛋白。初步结果表明， 用炎症剂处理培养的星形细胞瘤细胞既有 超氧化物的产生和线粒体DNA水平的显著增加 删除。建议通过以下方法来衡量这两种超氧化物的产量 培养的星形细胞瘤和神经细胞，以及mtDNA缺失水平 对炎性刺激的反应以确定是否存在相关性 超氧化物的产生和线粒体DNA缺失的程度之间的关系。这些 实验可能会提供有关炎症作用的更多信息 阿尔茨海默病的病理生理学过程。

Recent results indicate that brain mitochondrial DNA (mtDNA) deletions increase with age and that these deletions are regionally variable. A 4977 basepair deletion in brain mtDNA was found to increase with age in basal ganglia, substantia nigra, and frontal cortex. In contrast few mtDNA deletions were found in cerebellum. Also levels of a 7463 basepair mtDNA deletion were found to increase with age in these brain regions. In addition, point mutations in codon 331 of brain mtDNA appear to be elevated in Alzheimer's disease. It is proposed to measure levels of brain mtDNA deletions 4977, 7463, and codon 331 point mutation in frontal cortex, medial temporal cortex, putamen, and cerebellum in brains from age-matched non-demented control subjects and Alzheimer's disease patients. Preliminary results indicate that these mtDNA deletions can be measured using a quantitative polymerase chain reaction method. It is proposed to compare normal and Alzheimer's disease brain for both the amount and regional specificity of mtDNA deletions. Attempts will be made to correlated pathological findings (e.g. plaque counts, neurofibrillary tangle counts) with the extent and distribution of mtDNA deletions. A possible source of mtDNA deletions is oxidative stress arising from inflammation. A variety of inflammatory agents stimulate cultured human astrocytoma cells to produce the cytokines interleukin-1 (IL-1) and interleukin-6 (IL-6). IL-6 promotes aberrant neuronal differentiation and aptosis. Both IL-6 and IL-1 promote the synthesis of the Alzheimer's disease beta-amyloid precursor protein. Preliminary results suggest that cultured astrcytoma cells treated with inflammatory agents have both a marked increase in superoxide production and increased levels of mtDNA deletions. It is proposed to measure both superoxide production by cultured astrocytoma and neuronal cells, and levels of mtDNA deletions in response to inflammatory stimuli to determine if there are correlations between superoxide production and the extent of mtDNA deletions. These experiments may provide additional information on the role of inflammatory processes in the pathophysiology of Alzheimer's disease.