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

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          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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          Author and article information

          Journal
          Nat Med
          Nature medicine
          Springer Science and Business Media LLC
          1078-8956
          1078-8956
          Dec 1999
          : 5
          : 12
          Affiliations
          [1 ] Department of Neurology, Columbia University, New York, New York 10032, USA.
          Article
          10.1038/70978
          10581083
          94a219b6-a420-4564-81a7-99c2624d68a8
          History

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