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3243445 
Journal Article 
Nitric oxide and reactive oxygen species in Parkinson's disease 
Tieu, K; Ischiropoulos, H; Przedborski, S 
2003 
Yes 
IUBMB Life
ISSN: 1521-6543
EISSN: 1521-6551 
55 
6 
329-335 
WOS:000184460000007 
Parkinson's disease is a neurodegenerative disorder of
unknown pathogenesis. Oxidative stress has been proposed as one of several pathogenic hypotheses.
Evidence for the participation of oxidative processes in the pathogenesis of Parkinson's disease
have been obtained in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model by the use of
genetically altered mice. MPTP administration has been shown to increase levels of superoxide
both intracellularly, via the inhibition of mitochondrial respiration and other mechanisms and
extracellularly, via the activation of NADPH-oxidase in microglia. In addition to superoxide,
nitric oxide production by nNOS or by microglial iNOS also contributes to the MPTP neurotoxocity.
Mice with endowed defences against superoxide or with deficiency in the nNOS and iNOS are
protected from MPTP toxicity suggesting that formation of reactive oxygen and nitrogen
intermediates both intracellularly and extracellularly contributes to the demise of dopaminergic
neurons. Similar contribution of reactive nitrogen and oxygen species may well underlie the
neurodegenerative processes in Parkinson's disease. 
neurodegeneration; Parkinson's disease; MPTP; iNOS; ROS; NADPH-oxidase; peroxynitrite