Role of Nitric Oxide in MPTP-Induced Dopaminergic Neuron Degeneration
Abstract
This four year grant proposal investigates the role of nitric oxide (NO) in dopaminergic (DA) neuron death in the MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) mouse model of Parkinson's Disease (PD). The PI's work suggests that both superoxide radicals and nitric oxide (NO) contribute to MPTP toxicity. Using this mouse model of PD, Specific Aim (SA) I identifies which nitric oxide synthase (NOS) enzyme is the main culprit in the death of DA neurons in the substantia nigra of MPTP-treated mice. SA II (1) characterizes the upregulation of iNOS following MPTP in wild-type mice, and (2) assesses the effects of MPTP on the nigrostriatal DA pathway of iNOS ko mice. SA III quantifies brain levels of dityrosine and nitrotyrosine, main markers of the deleterious effects of peroxynitrite on brain proteins while SA-IV assesses several candidate proteins and identifies others that are at risk of oxidative/nitrative attack following MPTP administration. All of our data confirm that both the superoxide radical and NO are indeed involved in the MPTP neurotoxic process in the SNpc of mice and point to peroxynitrite, the product of the superoxide radical/NO reaction, as the agent most likely damaging these DA neurons.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2003
- Accession Number
- ADA420096
Entities
People
- Serge Przedborski
- Vernice Jackson-lewis
Organizations
- Columbia University