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Oligodendrocyte-formed myelin sheaths allow fast synaptic transmission in the brain and their degeneration leads to demyelinating diseases such as multiple sclerosis.Remyelination requires the differentiation of oligodendrocyte progenitor cells into mature oligodendrocytes but,in chronic neurodegenerative disorders,remyelination fails due to adverse environment.Therefore,a strategy to prompt oligodendrocyte progenitor cell differentiation towards myelinating oligodendrocytes is required.The neuromodulator adenosine,and its receptors(A1,A2A,A2B and A3 receptors:A1R,A2AR,A2BR and A3R),are crucial mediators in remyelination processes.It is known that A1Rs facilitate oligodendrocyte progenitor cell maturation and migration whereas the A3Rs initiates apoptosis in oligodendrocyte progenitor cells.Our group of research contributed to the field by demonstrating that A2AR and A2BR inhibit oligodendrocyte progenitor cell maturation by reducing voltage-dependent K+currents necessary for cell differentiation.The present review summarizes the possible role of adenosine receptor ligands as potential therapeutic targets in demyelinating pathologies such as multiple sclerosis.