Studies on the pathogenesis of Parkinson's disease in Japan
Abstract
Studies on the pathogenesis of nigral cell death in Parkinson's disease (PD) are reviewed. Discussions are focused mainly on studies performed by Japanese investigators because of the purpose of this issue. We and other groups found a decrease in complex I of the mitochondrial electron transfer complex in the substantia nigra of patients with PD, and in addition to complex I deficiency, we reported loss of alpha-ketoglutarate dehydrogenase complex of the tricarboxylic acid cycle (TCA cycle) by immunohistochemistry. Thus mitochondrial respiratory failure and resultant energy crisis appear to be one of the most important mechanisms that lead nigral neurons to cell death. The primary cause of mitochondrial respiratory failure has not been elucidated yet; however, environmental neurotoxins such as 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) may be responsible for nigral cell death in PD; in this respect a number of candidate toxins including tetrahydroisoquinolines and beta-carbolines have extensively been studied for nigral as well as mitochondrial toxicity. Recent progress in this field is also reviewed. Even if an environmental neurotoxin is involved in PD, exposure to such a neurotoxin alone may not account for its path...Continue Reading
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