POINT MUTATIONS OF MITOCHONDRIAL GENOME IN PARKINSONS-DISEASE

被引:135
作者
IKEBE, S
TANAKA, M
OZAWA, T
机构
[1] NAGOYA UNIV,FAC MED,DEPT BIOMED CHEM,SHOWA KU,NAGOYA,AICHI 466,JAPAN
[2] JUNTENDO UNIV,SCH MED,DEPT NEUROL,TOKYO 113,JAPAN
来源
MOLECULAR BRAIN RESEARCH | 1995年 / 28卷 / 02期
关键词
PARKINSONS DISEASE; MITOCHONDRION; MITOCHONDRIAL DNA; NIGROSTRIATAL PATHWAY; OXIDATIVE DAMAGE; POINT MUTATION; COMPLEX I; NADH DEHYDROGENASE;
D O I
10.1016/0169-328X(94)00209-W
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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.
引用
收藏
页码:281 / 295
页数:15
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