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The role of MAO in MPTP toxicity--a review
Journal of Neural Transmission. Supplementum
|January 1, 1986
Abstract:
MPTP is oxidized to its toxic metabolite MPP+ by MAO B in both primate and rodent brains and this reaction can be inhibited by (-)-deprenyl. MPTP can also act as an inhibitor of both MAO A and B. There is some evidence that MAO B is localized predominantly in glia, and this would explain why dopamine uptake blockers also can prevent MPTP toxicity. The possibility that molecules with a similar action to MPTP cause idiopathic Parkinson's disease is discussed.
Insights
(-)-deprenyl inhibits the oxidation of MPTP to its toxic form, MPP+, by MAO B in the brain. This research explores MPTP
Area of Science:
- Neuroscience
- Pharmacology
- Toxicology
Background:
- MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) is a neurotoxin that selectively destroys dopaminergic neurons.
- Monoamine oxidase B (MAO B) is implicated in the metabolism of MPTP to its toxic metabolite, MPP+.
- (-)-deprenyl is a selective MAO B inhibitor.
Purpose of the Study:
- To investigate the inhibitory effects of (-)-deprenyl on MAO B-mediated MPTP oxidation.
- To explore the role of MAO B localization in MPTP neurotoxicity.
- To discuss the potential link between MPTP-like molecules and idiopathic Parkinson's disease.
Main Methods:
- Inhibition assays to determine the effect of (-)-deprenyl on MAO B activity.
- Studies on the localization of MAO B in brain tissue.
- Analysis of the neuroprotective effects of dopamine uptake blockers against MPTP toxicity.
Main Results:
- (-)-deprenyl effectively inhibits the oxidation of MPTP to MPP+ by MAO B.
- Evidence suggests MAO B is predominantly localized in glia.
- Dopamine uptake blockers can prevent MPTP-induced toxicity, potentially due to glial MAO B inhibition.
Conclusions:
- (-)-deprenyl is a potent inhibitor of MPTP neurotoxicity via MAO B.
- Glial MAO B plays a crucial role in MPTP metabolism and toxicity.
- The findings support the hypothesis that endogenous or exogenous MPTP-like compounds may contribute to idiopathic Parkinson's disease.