Oligodendrocyte precursor cell maturation: role of adenosine receptors

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, A_2A, A_2B and A₃ receptors: A₁R, A_2AR, A_2BR 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 A_2AR and A_2BR 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.