Mitochondrial dysfunction - A pathogenetic factor in Parkinson's disease

The cause of Parkinson's disease is still unknown. Nonetheless, there are s ome generally accepted hypotheses with respect to the cascade of dopaminerg ic cell degeneration. One of the factors is a decrease in respiratory chain complex I activity. This enzyme abnormality is only found in substantia ni gra pars compacta. It is not currently known whether this is due to a genet ic abnormality of the nuclear or mitochondrial genome or to an exo- or endo toxin. To date, no specific abnormality of the mitochondrial genome has bee n detected, although ageing leads to deletions in up to 5% of all mitochond rial genome molecules in the brain. There is controversy whether this compl ex I defect is also detectable in muscle or blood cells. It is our convicti on that the considerable overlap between blood cells from normal controls a nd patients with Parkinson's disease means that such measurements are not d istinctive for the two conditions. A decrease in complex I activity in post mitotic cells may be one of the crucial factors for cell death.