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[A susceptible factor to acquire parkinsonism: sparteine oxidation polymorphism]
Abstract:
Recently, we found that hepatic oxidative enzyme(s) functions to attenuate neurotoxic effects of MPTP by converting the agent to its inactive metabolite(s) and reducing the amount of MPTP reaching at the brain in mice. Since the factors affecting the neurotoxic effects of MPTP may be related to the cause of spontaneous Parkinsonism, we studied the oxidation polymorphism of sparteine in 49 patients with parkinsonism. Although no poor metabolizer was found in patients with Parkinsonism, mean metabolic ratio of the patients was significantly (P less than 0.05) greater than that of healthy subjects. Furthermore, the value showed a significantly negative correlation (r = -0.327, p less than 0.05) with the onset of age. In addition, the percentage of the presumed heterozygotes (metabolic ratio less than 1.4) was tended to be greater in the patients with the onset of age, younger than 49 years (10/31) than in those with the onset of age, older than 50 years (2/18). These results suggest that decreased capacity of sparteine oxidation may be one of the susceptible factors to acquire Parkinsonism in human.
Insights
Decreased sparteine oxidation capacity may increase Parkinsonism risk. This study found impaired metabolism in parkinsonism patients, suggesting a link to disease susceptibility.
Area of Science:
- Neuroscience
- Pharmacology
- Genetics
Context:
- Hepatic oxidative enzymes metabolize MPTP, reducing neurotoxicity.
- Parkinsonism shares potential etiological factors with MPTP neurotoxicity.
- Sparteine oxidation serves as a probe for drug-metabolizing enzyme activity.
Purpose:
- To investigate the role of sparteine oxidation polymorphism in the susceptibility to Parkinsonism.
- To explore the relationship between metabolic capacity and age of onset in Parkinson's disease patients.
Summary:
- This study examined sparteine oxidation in 49 Parkinsonism patients.
- While no poor metabolizers were identified, patients showed a significantly higher mean metabolic ratio than healthy controls.
- A negative correlation was observed between metabolic ratio and age of onset, with younger-onset patients exhibiting a higher prevalence of presumed heterozygotes.
Impact:
- Results suggest that reduced sparteine oxidation capacity is a potential susceptibility factor for developing Parkinsonism.
- This finding may contribute to understanding the genetic and metabolic underpinnings of Parkinson's disease.
- Further research into drug metabolism polymorphisms could offer insights into personalized Parkinson's disease risk assessment.