Neuroprotection by (R)-deprenyl and 7-nitroindazole in the MPTP C57BL/6 mouse model of neurotoxicity.

Abstract

The neurodegenerative properties of the parkinsonian inducing agent 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) are thought to result from inhibition of complex I of the mitochondrial respiratory chain by the monoamine oxidase-B (MAO-B) generated 1-methyl-4-phenylpyridinium metabolite MPP+. 7-Nitroindazole (7-NI) both a reversible MAO-B inhibitor and a neuronal nitric oxide synthase (nNOS) inhibitor, and (R)-deprenyl a potent MAO-B inactivator, provide neuroprotection in the C57BL/6 mouse model of MPTP neurotoxicity. The results reported here demonstrate the complexities of the effects of 7-NI in this model and examine the possibility of other mechanisms of neuroprotection by (R)-deprenyl.