Exploring the functions of selected histone demethylases in myelinating cells

外周和中枢神经系统（分别为PNS和CNS）由以电信号形式携带信息的神经元和在支持神经元功能中具有多种作用的神经胶质细胞构成。在这个项目中，我们特别感兴趣的是髓鞘神经胶质细胞的功能，它在神经元的轴突部分周围建立了一个富含脂质的厚髓鞘，以隔离轴突，保护它们免受外部环境的影响，并允许电信号沿着轴突快速传导。存在两种类型的髓鞘形成细胞，PNS中的雪旺细胞和CNS中的少突胶质细胞。在病变的情况下，许旺细胞有能力改变它们的身份以失去它们的髓鞘并转化为刺激轴突再生并引导轴突再生到它们以前的目标的修复细胞。一旦轴突再生，许旺细胞就在再生的轴突周围重建髓鞘。在中枢神经系统中，髓鞘生成少突胶质细胞不具有转化为修复细胞的能力，并且不能刺激轴突再生。此外，他们的髓鞘含有蛋白质，发送轴突再生的负信号，从而阻止再生。然而，在某些情况下，中枢神经系统病变只是脱髓鞘：它们导致少突胶质细胞死亡，但保留轴突完整。这种类型的病变发生在称为多发性硬化症的CNS退行性疾病的过程中。在这种情况下，可以发生髓鞘再生，但这个过程的效率是有限的，在疾病开始时是有效的，随着疾病的进展和患者的年龄变得低效。多发性硬化症是最常见的中枢神经系统退行性疾病，目前尚无有效的治疗方法。在PNS中，损伤后的轴突再生和髓鞘再生也是年龄依赖性的，在老年个体中变得不那么有效。因此，确定改善轴突再生和髓鞘再生的治疗方法是至关重要的。我们的工作表明，一种称为染色质重塑酶的蛋白质可以控制我们基因的激活，可以用来提高损伤后的再生效率。该项目将分析选定的染色质重塑酶（称为组蛋白脱甲基酶）参与雪旺细胞和少突胶质细胞的发育以及PNS和CNS在PNS创伤性病变和CNS脱髓鞘病变后的再生过程。

The peripheral and central nervous systems (PNS and CNS, respectively) are constituted of neurons that carry the information in the form of electric signals, and of glial cells that have multiple roles in supporting neuronal functions. In this project, we are particularly interested in the functions of myelinating glial cells that build a thick myelin sheath rich in lipids around the axonal part of neurons to insulate axons, protect them from the external environment and allow fast conduction of electric signals along axons. Two types of myelinating cells exist, Schwann cells in the PNS and oligodendrocytes in the CNS. In case of a lesion, Schwann cells have the ability to change their identity to lose their myelin and convert into a repair cell that stimulates axonal regeneration and guide the regrowth of axons to their former target. Once axons have regrown, Schwann cells rebuild a myelin sheath around regenerated axons. In the CNS, myelinating oligodendrocytes do not have the ability to convert into repair cells and cannot stimulate axonal regrowth. In addition, their myelin contains proteins that send negative signals for axonal regrowth, thereby preventing regeneration. However, there are some cases where CNS lesions are only demyelinating: they lead to oligodendrocyte death, but leave axons intact. This type of lesion occurs in the course of a CNS degenerative disease called multiple sclerosis. In this case, remyelination can occur, but the efficiency of this process is limited, being efficient at the start of the disease and becoming inefficient as the disease progresses and with the age of the patient. Multiple sclerosis is the most frequent degenerative disease of the CNS and there is currently no available cure. In the PNS, axonal regeneration and remyelination after lesion are also age-dependent, becoming less efficient in old individuals. It is thus of utmost importance to identify treatments to improve axonal regeneration and remyelination. Our work shows that a type of proteins called chromatin-remodeling enzymes, which can control the activation of our genes, could be used to increase the efficiency of regeneration after lesion. This project will analyze the involvement of selected chromatin-remodeling enzymes called histone demethylases, in the development of Schwann cells and oligodendrocytes and in the regeneration process of the PNS and CNS after a traumatic lesion in the PNS and after a demyelinating lesion in the CNS.