Journal
NEURAL REGENERATION RESEARCH
Volume 16, Issue 9, Pages 1686-1692Publisher
WOLTERS KLUWER MEDKNOW PUBLICATIONS
DOI: 10.4103/1673-5374.306058
Keywords
adenosine receptors; K+ channels; oligodendrocyte differentiation; oligodendrocyte progenitor cells; remyelination
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Funding
- University of Florence (Fondi Ateneo) [PRIN 2015E8EMCM_002]
- Fondazione Italiana Sclerosi Multipla (FISM) [2019/R-Single/036]
- Fondazione Umberto Veronesi
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Oligodendrocyte-formed myelin sheaths facilitate fast synaptic transmission in the brain, but their degeneration can lead to demyelinating diseases. Remyelination relies on the differentiation of oligodendrocyte progenitor cells into mature oligodendrocytes, with the neuromodulator adenosine and its receptors playing crucial roles in this process. The review highlights the potential therapeutic targets in demyelinating pathologies like multiple sclerosis by targeting adenosine receptor ligands.
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 (A(1), A(2A), A(2B) and A(3) receptors: A(1R), A(2A)R, A(2B)R and A(3)R), are crucial mediators in remyelination processes. It is known that A(1)Rs facilitate oligodendrocyte progenitor cell maturation and migration whereas the A(3)Rs initiates apoptosis in oligodendrocyte progenitor cells. Our group of research contributed to the field by demonstrating that A(2A)R and A(2B)R 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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