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Lack of remyelination is primarily attributed to the failure of oligodendrocyte progenitor cells (OPCs) to differentiate into mature oligodendrocytes. The neuromodulator adenosine can influence OPC differentiation, and by selectively stimulating A\n                    <jats:sub>2A<\/jats:sub>\n                    and A\n                    <jats:sub>2B<\/jats:sub>\n                    receptors (A\n                    <jats:sub>2A<\/jats:sub>\n                    R, A\n                    <jats:sub>2B<\/jats:sub>\n                    R), it inhibits OPC maturation. In the efforts of developing remyelinating and neuroprotective agents, this study evaluated the ability of a novel dual A\n                    <jats:sub>2A<\/jats:sub>\n                    R\/A\n                    <jats:sub>2B<\/jats:sub>\n                    R antagonist, P626, in the experimental autoimmune encephalomyelitis (EAE) mouse model and cultured OPCs. EAE mice, 14\u2009days after MOG\n                    <jats:sub>35\u201355<\/jats:sub>\n                    immunisation, received intranasal administration of P626 for 2\u2009weeks, which improved motor symptoms, as evidenced by reduced clinical scores and enhanced performance on the rotarod test, and alleviated thermal and mechanical hypersensitivity without significantly affecting body weight. In spinal cord sections, P626 protected from the reduction of Luxol Fast Blue staining and increased myelin basic protein staining in immunohistochemical analysis. Patch\u2010clamp experiments on cultured OPCs exposed to high extracellular adenosine concentrations demonstrated that P626 prevented the A\n                    <jats:sub>2A<\/jats:sub>\n                    R\u2010 and A\n                    <jats:sub>2B<\/jats:sub>\n                    R\u2010mediated reduction in sustained\n                    <jats:italic>I<\/jats:italic>\n                    <jats:sub>\n                      <jats:italic>K<\/jats:italic>\n                    <\/jats:sub>\n                    and transient\n                    <jats:italic>I<\/jats:italic>\n                    <jats:sub>\n                      <jats:italic>A<\/jats:italic>\n                    <\/jats:sub>\n                    currents, both essential for cell differentiation. In conclusion, P626 showed efficacy in reducing neurological symptoms and demyelination in an MS model.\n                  <\/jats:p>","DOI":"10.1111\/jcmm.70952","type":"journal-article","created":{"date-parts":[[2025,11,18]],"date-time":"2025-11-18T06:45:14Z","timestamp":1763448314000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Protection From Demyelination by the Novel Adenosine Dual\n                    <scp>\n                      A\n                      <sub>2A<\/sub>\n                    <\/scp>\n                    \/\n                    <scp>\n                      A\n                      <sub>2B<\/sub>\n                    <\/scp>\n                    Receptor Antagonist\n                    <scp>P626<\/scp>\n                    in\n                    <scp>EAE<\/scp>\n                    and Cultured Oligodendrocyte Precursor 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