en Cell, Stem Cell and Cancer Cell, Stem Cell and Cancer Experimental research article Experimental research article <div style="text-align: justify;"><strong><span class="fontstyle0">Introduction: </span></strong><span class="fontstyle2">Adipose-derived stem cells (ADSCs) are one of the most well-known and accessible sources of stem cells that can be used for the treatment of neurodegenerative diseases. On the other hand, previous studies have suggested that selegiline, as an irreversible inhibitor of monoamine oxidase, affects stem cells&rsquo; differentiation into neurons. This study was conducted to investigate the involvement in phosphatidylinositol-bisphosphate 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) pathways in ADSCs differentiation to neuron-like cells using selegiline as inducer. </span><span class="fontstyle0"><strong>Methods:</strong> </span><span class="fontstyle2">ADSCs were isolated from male rats, cultured in DMEM and then treated with selegiline (10</span><span class="fontstyle2" style="font-size:6pt;">-7 </span><span class="fontstyle2">M) for 24h. Real-time PCR for nestin and neurofilament-68 (NF-68) was performed from the negative control (ADSCs at the 3</span><span class="fontstyle2" style="font-size:6pt;">rd </span><span class="fontstyle2">passage), positive control (ADSCs were treated with 10</span><span class="fontstyle2" style="font-size:6pt;">-7 </span><span class="fontstyle2">M selegeline for 24h, PI3AKT inhibitor (ADSCs were pretreated with treated with 10&micro;M LY294002 for 3h, then10</span><span class="fontstyle2" style="font-size:6pt;">-7 </span><span class="fontstyle2">M selegeline for the next 24h, and MAPK inhibitor (ADSCs were pretreated with treated with 10&micro;M PD98059 for 3h, then10</span><span class="fontstyle2" style="font-size:6pt;">-7 </span><span class="fontstyle2">M selegeline for the next 24h). </span><strong><span class="fontstyle0">Results: </span></strong><span class="fontstyle2">Nestin and NF-68 genes have been over-expressed in the selegiline-treated ADSCs. The PD98059 and LY294002 significantly down-regulated the selegiline-induced over-expression of nestin and NF-68; however, PI3K inhibition did not return the genes expression to control level. ADSCs were immunoreactivefor nestin and NF-68 about 98% and 95% respectively. </span><strong><span class="fontstyle0">Conclusion: </span></strong><span class="fontstyle2">According to the results, selegilinecan induce the gene expression of neural stem cell biomarkers in ADSCs through MAPK pathway activating and so differentiating them into neuron-like cells.</span></div> Selegiline, Adipose-derived stem cells, Neuron-like cells, MAPK. 79 87 http://ppj.phypha.ir/browse.php?a_code=A-10-839-3&slc_lang=en&sid=1 Alireza Abdanipour 3200319475328460030706 3200319475328460030706 No Department of Anatomical Sciences, Faculty of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran Maedeh Amalavar 3200319475328460030707 3200319475328460030707 No Department of Physiology, Faculty of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran Mohsen Alipour 3200319475328460030708 3200319475328460030708 No Department of Physiology, Faculty of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran Hadi Feizi hfeizik@zums.ac.ir 3200319475328460030709 3200319475328460030709 Yes Department of Physiology, Faculty of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran