Ikebe S, Tanaka M, Ozawa T
Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan.
Brain Res Mol Brain Res. 1995 Feb;28(2):281-95. doi: 10.1016/0169-328x(94)00209-w.
Oxidative stress and subsequent energy crisis have been proposed as the cause of nigral neuronal cell death in Parkinson's disease. We have reported defects in the mitochondrial respiratory chain and increased amount of deleted mitochondrial genome in the nigrostriatal system of patients with Parkinson's disease. Deletion in mitochondrial DNA could be ascribed to somatically acquired premature aging leading to cell death. To elucidate the contribution of maternally transmitted point mutations in mitochondrial DNA to the premature DNA damages, we employed a direct sequencing system and analyzed the total nucleotide sequences of mitochondrial DNA in the brains of five patients with idiopathic Parkinson's disease. There were no predominant point mutations among the patients in contrast to some neuromuscular diseases. However, each patient had several point mutations that would result in a significant change in the gene products. Some of these mutations may be involved either in the increased production of oxygen radicals from the mitochondrial respiratory chain or in the increased susceptibility of the respiratory chain components to oxidative damage. We propose that some of these mutations can be regarded as one of the risk factors accelerating degeneration of nigrostriatal pathway in Parkinson's disease.
氧化应激及随后的能量危机被认为是帕金森病黑质神经元细胞死亡的原因。我们曾报道帕金森病患者黑质纹状体系统存在线粒体呼吸链缺陷以及缺失型线粒体基因组数量增加。线粒体DNA的缺失可能归因于体细胞获得性早衰，进而导致细胞死亡。为阐明线粒体DNA母系传递的点突变对DNA过早损伤的作用，我们采用直接测序系统，分析了5例特发性帕金森病患者大脑中线粒体DNA的全核苷酸序列。与某些神经肌肉疾病不同，这些患者中没有占主导地位的点突变。然而，每位患者都有几个点突变，这些突变会导致基因产物发生显著变化。其中一些突变可能与线粒体呼吸链氧自由基生成增加有关，或者与呼吸链成分对氧化损伤的易感性增加有关。我们认为，这些突变中的一些可被视为加速帕金森病黑质纹状体通路退变的危险因素之一。
