Targeting reactive oxygen species, reactive nitrogen species and inflammation in MPTP neurotoxicity and Parkinson's disease

Parkinson's disease (PD) is the second most frequent neurodegenerative disorder after Alzheimer's disease. The main clinical features of PD include tremor, bradykinesia, rigidity and postural instability. The primary pathology of PD is degeneration of dopaminergic neurons in the substantia nigra pars compacta, resulting in loss of the nigrostriatal pathway and a reduction of dopamine contents in the striatum. The biochemical and cellular changes that occur following the administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) are remarkably similar to that seen in idiopathic PD. Recent evidence shows that oxidative stress contributes to the cascade leading to dopaminergic cell degeneration in PD. However, oxidative stress is intimately linked to other components of neurodegenerative process, such as nitric oxide stress and inflammation. Recently, there is convincing evidence for the involvement of nitric oxide that reacts with superoxide to produce peroxynitrite and ultimately hydroxyl radical production. In view of these new insights, however, the role of reactive nitrogen species, reactive oxygen species and inflammation against MPTP neurotoxicity is not fully understood. In this review, we discuss the possible role of reactive nitrogen species, reactive oxygen species and inflammation in the dopaminergic neurons against MPTP neurotoxicity.