Role of Nitric Oxide in MPTP Induced Dopaminergic Neuron
Abstract
The oxidative stress hypothesis of Parkinson's disease (PD) is thought to involve the superoxide radical and nitric oxide (NO). MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) a meperidine analog, mimics most of the hallmarks of PD and is an important tool that is used to give insights into this debilitating disease. Previous evidence from our laboratory has shown that the superoxide radical is involved in the MPTP neurotoxic process. Herein, we demonstrate a robust gliosis in the substantia nigra of the MPTP-treated mouse which is associated with the marked up-regulation of inducible nitric oxide synthase (iNOS). We also show that mutant mice devoid of the iNOS gene are significantly more resistant to MPTP's toxic effects. These results point to NO as a possible culprit in the MPTP neurotoxic process. In keeping with our hypothesis that NO is part of the oxidative stress hypothesis, we show that MPTP induces, in those brain areas most susceptible to its toxic effects, the formation of 3-nitrotyrosine, o,o-dityrosine and ortho-tyrosine, three stable markers of protein nitration and oxidation
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2000
- Accession Number
- ADA384796
Entities
People
- Serge E. Przedborski
Organizations
- Columbia University