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J Cell Physiol. 2019 Jan 8. doi: 10.1002/jcp.27774. [Epub ahead of print]

Small molecule of sphingosine as a rescue of dopaminergic cells: A cell therapy approach in neurodegenerative diseases therapeutics.

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Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran.
Pharmaceutical Sciences Research Center, Pharmaceutical Sciences Branch, Islamic Azad University Tehran Medical Unit, Tehran, Iran.
Department of Biology, Faculty of Sciences, Shahid Chamran University of Ahvaz, Ahvaz, Iran.
School of Medicine, Kashan University of Medical Sciences, Isfahan, Iran.
Department of Neuroscience, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran.
Department of Tissue Engineering and Applied Cell Sciences, Faculty of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.
School of Advanced medical sciences, Stem Cell And Regenerative Medicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran.


Multiple sclerosis (MS) patients should take medication such as fingolimod (FTY-720) for a long time, hence pharmaceutical effects on other neural cells such as dopaminergic cells are important. Dopaminergic cell line, BE(2)-M17, was treated by FTY-720 and then cell viability and genes involve in neurosurvival were investigated. It was disclosed that FTY-720 significantly stimulates Bcl2 overexpression. Whereas, it decreased intracellular reactive oxygen species production and cell membrane damage of dopaminergic cells. The increase in Bcl2/Bax ratio increased the cell metabolic activity and decreased propidium iodide-positive cells. Besides, FTY-720 induced the overexpression of CACNA1C, nNOS gene, and nitric oxide production. However, FTY-720 induced GABARA1 overexpression and eventually it could overcame to the cytotoxic effect of intracellular calcium. This cascade led to tyrosine hydroxylase and BDNF genes overexpression whereas FTY-720 did not change GDNF concentration in BE(2)-M17 cells. Concluding, it might be said that taking FTY-720 in MS patients did not induce adverse effect on dopaminergic cells.


FTY-720/ fingolimod; GDNF; MS patients; dopaminergic cells; neural survival


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