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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 

Inhibition of monoamine oxidase contributes to the protective effect of 7-nitroindazole against MPTP neurotoxicity.

The ability of 7-nitroindazole (7-NI) to protect against MPTP-induced neurotoxicity has been attributed to its inhibition of neuronal nitric oxide synthase. In the present study, 7-NI was found to counteract almost completely striatal dopamine depletion caused by a single subcutaneus injection of 20 mg/kg MPTP in mice. This effect, however, was accompanied by a significant reduction in the striatal levels of MPP+, the toxic metabolite generated via monoamine oxidase B-catalyzed MPTP oxidation. In the presence of 7-NI, a dose of 40 mg/kg MPTP produced MPP concentrations similar to those measured after treatment with 20 mg/kg MPTP alone. A comparison of neurotoxicity in these two experimental conditions (i.e., mice treated with 20 mg/kg alone versus 40 mg/kg MPTP plus 7-NI) revealed only a slight (20%), but statistically significant, protection of dopamine depletion with 7-NI. These data indicate that the mechanism by which 7-NI counteracts MPTP neurotoxicity in mice is not due solely to inhibition of neuronal nitric oxide synthase, but involves a reduction in MPP+ formation.[1]

References

  1. Inhibition of monoamine oxidase contributes to the protective effect of 7-nitroindazole against MPTP neurotoxicity. Di Monte, D.A., Royland, J.E., Anderson, A., Castagnoli, K., Castagnoli, N., Langston, J.W. J. Neurochem. (1997) [Pubmed]
 
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