PDF(Sci-hub)
Abstract：
Multiple sclerosis (MS) is the most demyelinating disease of the central nervous system (CNS) characterized by neuroinflammation. Oligodendrocyte progenitor cells (OPCs) are cycling cells in the developing and adult CNS that, under demyelinating conditions, migrate to the site of lesions and differentiate into mature oligodendrocytes to remyelinate damaged axons. However, this process fails during disease chronicization due to impaired OPC differentiation. Moreover, OPCs are crucial players in neuro-glial communication as they receive synaptic inputs from neurons and express ion channels and neurotransmitter/neuromodulator receptors that control their maturation. Ion channels are recognized as attractive therapeutic targets, and indeed ligand-gated and voltage-gated channels can both be found among the top five pharmaceutical target groups of FDA-approved agents. Their modulation ameliorates some of the symptoms of MS and improves the outcome of related animal models. However, the exact mechanism of action of ion-channel targeting compounds is often still unclear due to the wide expression of these channels on neurons, glia, and infiltrating immune cells. The present review summarizes recent findings in the field to get further insights into physio-pathophysiological processes and possible therapeutic mechanisms of drug actions.
摘要：
多发性硬化(MS)是以神经炎症为特征的中枢神经系统(CNS)的最脱髓鞘疾病。少突胶质祖细胞(OPCs)是发育中和成体中枢神经系统中的循环细胞,在脱髓鞘条件下，迁移到病变部位，分化为成熟的少突胶质细胞，再髓鞘损伤的轴突。然而,由于OPC分化受损，该过程在疾病慢性化过程中失败。此外，OPCs是神经胶质通讯中的关键参与者，因为它们从神经元接收突触输入并表达离子通道和控制其成熟的神经递质/神经调质受体。离子通道被认为是有吸引力的治疗靶点，事实上，配体门控和电压门控通道都可以在FDA批准的药物的前五个药物目标组中找到。它们的调节改善了MS的一些症状并改善了相关动物模型的结果。然而,由于这些通道在神经元上的广泛表达，离子通道靶向化合物的确切作用机制通常仍不清楚，glia,和浸润免疫细胞。本综述总结了该领域的最新发现，以进一步了解生理病理生理过程和药物作用的可能治疗机制。
