Selegiline, the irreversible inhibitor of
monoamine oxidase B (
MAO-B), is currently used to treat
Parkinson's disease. However, the mechanism of action of
selegiline is complex and cannot be explained solely by its
MAO-B inhibitory action. It stimulates gene expression, as well as expression of a number of mRNAs or
proteins in nerve and glial cells. Direct neuroprotective and anti-apoptotic actions of
selegiline have previously been observed in vitro. Previous studies showed that
selegiline can induce neuronal phenotype in cultured bone marrow stem cells and embryonic stem cells.
Embryonal carcinoma (EC) cells are developmentally pluripotene cells which can be differentiated into all cell types under the appropriate conditions. The present study was carried out to examine the effects of
selegiline on undifferentiated P19 EC cells. The results showed that
selegiline treatment had a dramatic effect on neuronal morphology. It induced the differentiation of EC cells into neuron-like cells in a concentration-dependent manner. The peak response was in a dose of
selegiline significantly lower than required for
MAO-B inhibition. The differentiated cells were immunoreactive for neuron-specific
proteins,
synaptophysin, and β-III
tubulin. Stem cell
therapy has been considered as an ideal option for the treatment of
neurodegenerative diseases. Generation of neurons from stem cells could serve as a source for potential
cell therapy. This study suggests the potential use of combined
selegiline and stem cell
therapy to improve deficits in
neurodegenerative diseases.