POINT MUTATIONS OF MITOCHONDRIAL GENOME IN PARKINSONS-DISEASE

Oxidative stress and subsequent energy crisis have been proposed as th e 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 d eath. To elucidate the contribution of maternally transmitted point mu tations in mitochondrial DNA to the premature DNA damages, we employed a direct sequencing system and analyzed the total nucleotide sequence s of mitochondrial DNA in the brains of five patients with idiopathic Parkinson's disease. There were no predominant point mutations among t he 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 mitocho ndrial respiratory chain or in the increased susceptibility of the res piratory chain components to oxidative damage. We propose that some of these mutations can be regarded as one of the risk factors accelerati ng degeneration of nigrostriatal pathway in Parkinson's disease.