Pharmacotherapy of parkinson`s Disease

Intrinsically, the substantia nigra pars compacta (SNc) is a region characterized by high levels of oxidative stress because free radicals are generated from dopamine degradation (mediated by MAO; Figure 1). Several antioxidative molecules (e.g., glutathione) are present in the SNc to limit damage produced by free-radical reactions, but in PD, such protection might be overwhelmed or impaired. Thus, cellular damage from oxidant stress has long been discussed as an etiopathology component of PD. The SNc is also rich in iron and copper, essential cofactors in the biosynthesis and metabolism of dopamine. The oxidation-reduction cycle of iron can also generate free radicals and toxic metabolites (Fig. 1). In addition, apoptosis (programmed cell death), excitotoxicity, inflammation, mitochondrial dysfunction, nitric oxide toxicity, proteasomal dysfunction, and autophagic cellular mechanisms are also implicated etiopathology mechanisms in PD.