Clinical pharmacology and neuroprotection in Parkinson's disease.
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-synuclein, 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. Conventional approaches to studies that use large numbers of patients in search of small effects are costly and time consuming, and it would be impossible to test all the potentially valuable neuroprotective agents because of a lack of time, money, or subjects. As a translational research, it is more profitable to test agents in a small number of selected patients in search of a more neuroprotective effect. Well designed translational research might allow us to reduce the risk of missing a powerful neuroprotective treatment.
Nomoto
Masahiro
M
Department of Clinical Pharmacology and Therapeutics, Ehime University School of Medicine Ehime, Shitsukawa, Shigenobu, Ehime 791-0295, Japan. nomoto@m.ehime-u.ac.jp
D006801:Humans; D009410:Nerve Degeneration / Q000188:drug therapy* / Q000517:prevention & control; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D010300:Parkinson Disease / Q000188:drug therapy*
D018696:Neuroprotective Agents