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Regulation and signaling of the GPR17 receptor in oligodendroglial cells.
Glia ( IF 5.4 ) Pub Date : 2020-02-22 , DOI: 10.1002/glia.23807
Davide Lecca 1 , Stefano Raffaele 1 , Maria P Abbracchio 1 , Marta Fumagalli 1
Affiliation  

Remyelination, namely, the formation of new myelin sheaths around denuded axons, counteracts axonal degeneration and restores neuronal function. Considerable advances have been made in understanding this regenerative process that often fails in diseases like multiple sclerosis, leaving axons demyelinated and vulnerable to damage, thus contributing to disease progression. The identification of the membrane receptor GPR17 on a subset of oligodendrocyte precursor cells (OPCs), which mediate remyelination in the adult central nervous system (CNS), has led to a huge amount of evidence that validated this receptor as a new attractive target for remyelinating therapies. Here, we summarize the role of GPR17 in OPC function, myelination and remyelination, describing its atypical pharmacology, its downstream signaling, and the genetic and epigenetic factors modulating its activity. We also highlight crucial insights into GPR17 pathophysiology coming from the demonstration that oligodendrocyte injury, associated with inflammation in chronic neurodegenerative conditions, is invariably characterized by abnormal and persistent GPR17 upregulation, which, in turn, is accompanied by a block of OPCs at immature premyelinating stages. Finally, we discuss the current literature in light of the potential exploitment of GPR17 as a therapeutic target to promote remyelination.

中文翻译:

少突胶质细胞中 GPR17 受体的调节和信号传导。

髓鞘再生,即在裸露的轴突周围形成新的髓鞘,抵消轴突变性并恢复神经元功能。在理解这种再生过程方面取得了相当大的进展,该过程在多发性硬化症等疾病中经常失败,使轴突脱髓鞘并容易受到损害,从而促进疾病进展。介导成人中枢神经系统 (CNS) 髓鞘再生的少突胶质前体细胞 (OPCs) 子集上的膜受体 GPR17 的鉴定已导致大量证据证实该受体是一种新的有吸引力的髓鞘再生靶标疗法。在这里,我们总结了 GPR17 在 OPC 功能、髓鞘形成和髓鞘再生中的作用,描述了其非典型药理学、下游信号传导、以及调节其活性的遗传和表观遗传因素。我们还强调了对 GPR17 病理生理学的重要见解,因为少突胶质细胞损伤与慢性神经退行性疾病的炎症相关,总是以异常和持续的 GPR17 上调为特征,这反过来又伴随着未成熟的前髓鞘形成阶段的 OPC 块. 最后,我们根据 GPR17 作为促进髓鞘再生的治疗靶点的潜在利用来讨论当前的文献。反过来,伴随着未成熟的前髓鞘形成阶段的 OPC 块。最后,我们根据 GPR17 作为促进髓鞘再生的治疗靶点的潜在利用来讨论当前的文献。反过来,伴随着未成熟的前髓鞘形成阶段的 OPC 块。最后,我们根据 GPR17 作为促进髓鞘再生的治疗靶点的潜在利用来讨论当前的文献。
更新日期:2020-02-22
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