| Co-Investigator(Kenkyū-buntansha) |
MIKI Tetsuro Ehime University, School of Medicine, Professor, 医学部, 教授 (00174003)
OHASHI Kyouichi Hamamatsu Medical University, School of Medicine, Professor, 医学部・臨床薬理学, 教授 (20137714)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2003: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2002: ¥2,900,000 (Direct Cost: ¥2,900,000)
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| Research Abstract |
There has been significant progress in the study of the causes, the pathogenesis, and the mechanism of cell death in Parkinson's disease (PD). Mutations in single genes have been shown to cause PD, and accumulation of alpha-synuclein seems to be a clue to the pathogenesis of neurodegeneration. However, mutations of single genes account for only a small number of cases. Environmental factors seem to play a large role in the majority of cases of sporadic PD. Genetic factors may predispose patients to develop PD if combined with other gene mutations or environmental toxins. In an attempt to design a neuroprotective therapy, the pathogenesis of neurodegeneration, and the mechanism of cell death have been studied. Aggregation of insoluble alpha-syuclein, oxidant stress, mitochondrial dysfunction, excitotoxicity, and glia and inflammatory processes are all thought to contribute to the cell death process and agents that interfere with these events may be neuroprotective. The final culmination of these events is supposed to be the induction of apoptosis in nigral dopaminergic neurons and this too offers opportunities for providing neuroprotection. A large number of different approaches are under discussion in the hope of developing a neuroprotective therapy, using clinical indices and neuroimaging markers of nigral dopaminergic neurons. Administration of L-dopa and other antiparkinsonian agents reverse motor deficits of patients with Parkinson s disease, however, the response to the treatment varies depend on each individual patient. We studied pharmacokinetics of medicines and their effect on parkinsonian signs, and grouped patients through their characteristic reactions to the treatment. They are now studied on the polymorphism of transpoters at the intestine, the neuron or the kidney. These results will be compared with those of superhelthy persons with the age of more than 100, to find the key gene to cause Parkinson's disease.
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