Cherchi Federica, Pugliese Anna Maria, Coppi Elisabetta
Department of Neuroscience, Psychology, Drug Research and Child Health-Neurofarba-Division of Pharmacology and Toxicology, University of Florence, Florence, Italy.
Neural Regen Res. 2021 Sep;16(9):1686-1692. doi: 10.4103/1673-5374.306058.
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, A, A and A receptors: AR, AR, AR and AR), are crucial mediators in remyelination processes. It is known that ARs facilitate oligodendrocyte progenitor cell maturation and migration whereas the ARs initiates apoptosis in oligodendrocyte progenitor cells. Our group of research contributed to the field by demonstrating that AR and AR 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.
少突胶质细胞形成的髓鞘有助于大脑中的快速突触传递，其退化会导致诸如多发性硬化症等脱髓鞘疾病。再髓鞘化需要少突胶质细胞祖细胞分化为成熟的少突胶质细胞，但在慢性神经退行性疾病中，由于不利的环境，再髓鞘化失败。因此，需要一种促使少突胶质细胞祖细胞向髓鞘形成的少突胶质细胞分化的策略。神经调质腺苷及其受体（A1、A2A、A2B和A3受体：A1R、A2AR、A2BR和A3R）是再髓鞘化过程中的关键介质。已知A1R促进少突胶质细胞祖细胞的成熟和迁移，而A2BR会引发少突胶质细胞祖细胞的凋亡。我们的研究小组通过证明A1R和A2BR通过降低细胞分化所需的电压依赖性钾电流来抑制少突胶质细胞祖细胞的成熟，为该领域做出了贡献。本综述总结了腺苷受体配体作为多发性硬化症等脱髓鞘疾病潜在治疗靶点的可能作用。
