Inducible nitric oxide synthase stimulates dopaminergic neurodegeneration in the MPTP model of Parkinson disease

GT Liberatore, V Jackson-Lewis, S Vukosavic… - Nature medicine, 1999 - nature.com
GT Liberatore, V Jackson-Lewis, S Vukosavic, AS Mandir, M Vila, WG McAuliffe, VL Dawson
Nature medicine, 1999nature.com
Abstract MPTP (1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine) damages dopaminergic
neurons as seen in Parkinson disease. Here we show that after administration of MPTP to
mice, there was a robust gliosis in the substantia nigra pars compacta associated with
significant upregulation of inducible nitric oxide synthase (iNOS). These changes preceded
or paralleled MPTP-induced dopaminergic neurodegeneration. We also show that mutant
mice lacking the iNOS gene were significantly more resistant to MPTP than their wild-type …
Abstract
MPTP (1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine) damages dopaminergic neurons as seen in Parkinson disease. Here we show that after administration of MPTP to mice, there was a robust gliosis in the substantia nigra pars compacta associated with significant upregulation of inducible nitric oxide synthase (iNOS). These changes preceded or paralleled MPTP-induced dopaminergic neurodegeneration. We also show that mutant mice lacking the iNOS gene were significantly more resistant to MPTP than their wild-type littermates. This study demonstrates that iNOS is important in the MPTP neurotoxic process and indicates that inhibitors of iNOS may provide protective benefit in the treatment of Parkinson disease.
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