A possible novel pharmacological therapy for Parkinson's disease using the pleiotropic property of Selegiline

Monoamine oxidase type B (MAO-B) inhibitors have neuroprotective properties in addition to their primary pharmacologic function. We examined the effects of selegiline, an irreversible MAO-B inhibitor, on the expression levels of survivin mRNA and lipid peroxidation in the corpus striata of 1-methyl-4-phenyl 1,2,3,6 tetrahydropyridine (MPTP)-induccd Parkinsonian roice. Mice were treated with normal saline (vehicle as control), MPTP alone (30 mg/kg of body weight), MPTP with low-dose of selegiline (0-1 mg/kg of body weight), or MPTP with high-dose of selegiline (1.0 mg/kg of body weight). A consecutive 7-day oral treatment of MPTP alone d'd not influence survivin mRNA expression. Selegiline treatment together with MPTP significantly uprcgulated survivin expression at both low- and high-doses. Interestingly, lipid Peroxidation was significantly suppressed by a low-dose of selegiline but not by a high-dose. These results suggest that selegiline has Pleiotropic effects; the upregulation effects on survivin mRNA expression are likely to be '"dependent from its primary pharmacological Properties (MAO-B inhibition), whereas the inhibitory effects on lipid peroxidation seem to be associated with its primary pharmacological properties. In addition to conventional dopamine supplementation therapy, selegiline might serve as a novel pharmacological therapeutic strategy for Parkinson's disease through its antiapoptotic properties via survivin induction as well as its antioxidative properties.