Myelin is a dynamic membrane that is important for coordinating the fast propagation of action potentials along small or large caliber axons (0.1–10 μm) some of which extend the entire length of the spinal cord. Due to the heterogeneity of electrical and energy demands of the variable neuronal populations, the axo-myelinic and axo-glial interactions that regulate the biophysical properties of myelinated axons also vary in terms of molecular interactions at the membrane interfaces. An important topic of debate in neuroscience is how myelin is maintained and modified under neuronal control and how disruption of this control (due to disease or injury) can initiate and/or propagate neurodegeneration. One of the key molecular signaling cascades that have been investigated in the context of neural injury over the past two decades involves the myelin-associated inhibitory factors (MAIFs) that interact with Nogo receptor 1 (NgR1). Chief among the MAIF superfamily of molecules is a reticulon family protein, Nogo-A, that is established as a potent inhibitor of neurite sprouting and axon regeneration. However, an understated role for NgR1 is its ability to control axo-myelin interactions and Nogo-A specific ligand binding. These interactions may occur at axo-dendritic and axo-glial synapses regulating their functional and dynamic membrane domains. The current review provides a comprehensive analysis of how neuronal NgR1 can regulate myelin thickness and plasticity under normal and disease conditions. Specifically, we discuss how NgR1 plays an important role in regulating paranodal and juxtaparanodal domains through specific signal transduction cascades that are important for microdomain molecular architecture and action potential propagation. Potential therapeutics designed to target NgR1-dependent signaling during disease are being developed in animal models since interference with the involvement of the receptor may facilitate neurological recovery. Hence, the regulatory role played by NgR1 in the axo-myelinic interface is an important research field of clinical significance that requires comprehensive investigation.

髓磷脂是一种动态膜，对于协调动作电位沿小口径或大口径轴突（0.1–10μm）的快速传播非常重要，其中一些轴突延伸了脊髓的整个长度。由于可变神经元群体的电力和能量需求的异质性，调节有髓鞘轴突的生物物理特性的轴突-髓鞘和轴突-胶质相互作用在膜界面处的分子相互作用方面也不同。神经科学中一个重要的辩论主题是如何在神经元控制下维持和修饰髓磷脂，以及这种控制的破坏（由于疾病或损伤）如何引发和/或传播神经变性。在过去的二十年中，在神经损伤的背景下研究的关键分子信号级联之一涉及与​​Nogo受体1（NgR1）相互作用的髓鞘相关抑制因子（MAIF）。MAIF分子超家族中最主要的是网状家族蛋白Nogo-A，它被确立为神经突发芽和轴突再生的有效抑制剂。但是，NgR1的低估作用是其控制轴突-髓磷脂相互作用和Nogo-A特异性配体结合的能力。这些相互作用可能发生在调节其功能和动态膜结构域的轴突和轴突胶质突触处。本篇综述提供了神经元NgR1在正常和疾病条件下如何调节髓磷脂厚度和可塑性的综合分析。特别，我们讨论了NgR1如何通过特定的信号转导级联在调节旁节和近旁节的域中起重要作用，这些信号转导对于微域分子结构和动作电位的传播很重要。由于干扰受体的参与可能促进神经功能恢复，因此正在动物模型中开发了针对疾病期间靶向NgR1依赖性信号传导的潜在疗法。因此，NgR1在轴突-髓鞘界面中的调节作用是重要的临床研究领域，需要进行全面的研究。由于干扰受体的参与可能促进神经功能恢复，因此正在动物模型中开发了针对疾病期间靶向NgR1依赖性信号传导的潜在疗法。因此，NgR1在轴突-髓鞘界面中的调节作用是重要的临床研究领域，需要进行全面的研究。由于干扰受体的参与可能促进神经功能恢复，因此正在动物模型中开发了针对疾病期间靶向NgR1依赖性信号传导的潜在疗法。因此，NgR1在轴突-髓鞘界面中的调节作用是重要的临床研究领域，需要进行全面的研究。