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- Title
Inducible nitric oxide synthase stimulates dopaminergic neurodegeneration in the MPTP model of Parkinson disease.
- Authors
Liberatore, Gabriel T.; Jackson-Lewis, Vernice; Vukosavic, Slobodanka; Mandir, Allen S.; Vila, Miquel; McAuliffe, W. Geoffrey; Dawson, Valina L.; Dawson, Ted M.; Przedborski, Serge
- 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.
- Subjects
SUBSTANTIA nigra; NITRIC-oxide synthases; PARKINSON'S disease
- Publication
Nature Medicine, 1999, Vol 5, Issue 12, p1403
- ISSN
1078-8956
- Publication type
Article
- DOI
10.1038/70978