Inducible nitric oxide synthase stimulates dopaminergic neurodegeneration in the MPTP model of Parkinson disease |
| |
Authors: | Liberatore G T Jackson-Lewis V Vukosavic S Mandir A S Vila M McAuliffe W G Dawson V L Dawson T M Przedborski S |
| |
Affiliation: | Department of Neurology, Columbia University, New York, New York 10032, USA. |
| |
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. |
| |
Keywords: | |
本文献已被 PubMed 等数据库收录! |
|