Review: The Role of Adenosine Recptors in OPC Maturation

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NHE
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Review: The Role of Adenosine Recptors in OPC Maturation

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Oligodendrocyte precursor cell maturation: role of adenosine receptors
Neural Regen Res. 2021 Sep;16(9):1686-1692.

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.

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Figure 2: Effects of A1, A2A, A2B and A3 receptor (A1R, A2AR, A2BR and A3R) activation on oligodendrocyte precursor cells (OPCs) and intracellular pathways involved.
The activation of A1Rs by adenosine (ADO) or other receptor agonists facilitates myelin deposition by Gi coupling. The stimulation of Gs-coupled receptors A2AR and/or A2BR lead to adenylyl cyclase (AC) activation causing an increase in intracellular cyclic adenosine monophosphate (cAMP), which, in turn, closes IK channels and inhibits OPC differentiation possibly by a mechanism involving protein kinase A (PKA) activation. A2BR activation also induces a block in IA currents but the molecular mechanism/s are still unknown. A3R stimulation induces OPC apoptosis by activating the intrinsic pathway, i.e. through reactive oxygen species (ROS) production and activation of Bcl-2-associated X (Bax), p53-upregulated modulator of apoptosis (PUMA) and caspase 3/9 proteins.
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