Purpose of Review

Multiple sclerosis (MS) is the most common demyelinating disease of the central nervous system (CNS). Inflammatory attacks in MS lead to both demyelination and axonal damage. However, due to incomplete remyelination most MS lesions remain chronically demyelinated. In parallel, there is axonal degeneration in the CNS of MS patients, contributing to progressive disability. There are currently no approved therapies that adequately restore myelin or protect axons from degeneration. In this review, we will discuss the pathophysiology of axonal loss and chronic demyelination in MS and how understanding this pathophysiology is leading to the development of new MS therapeutics.

Recent Findings

Ongoing research into the function of oligodendrocytes and myelin has revealed the importance of their relationship with neuronal health. Demyelination in MS leads to a number of pathophysiologic changes contributing to axonal generation. Among these are mitochondrial dysfunction, persistent neuroinflammation, and the effects of reactive oxygen and nitrogen species. With this information, we review currently approved and investigational therapies designed to restore lost or damaged myelin and protect against neuronal degeneration.

Summary

The development of therapies to restore lost myelin and protect neurons is a promising avenue of investigation for the benefit of patients with MS.

中文翻译：

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多发性硬化症的慢性脱髓鞘和轴突变性：发病机理和治疗意义。

审查目的

多发性硬化症（MS）是最常见的中枢神经系统（CNS）脱髓鞘疾病。MS的炎症发作会导致脱髓鞘和轴突损伤。但是，由于髓鞘再生不完全，大多数MS病变仍保持慢性脱髓鞘。同时，MS患者中枢神经系统存在轴突变性，导致进行性残疾。当前没有批准的疗法可以充分恢复髓磷脂或保护轴突免于变性。在这篇综述中，我们将讨论MS中轴突丢失和慢性脱髓鞘的病理生理，以及如何理解这种病理生理如何导致新的MS治疗方法的发展。

最近的发现

正在进行的对少突胶质细胞和髓磷脂功能的研究揭示了它们与神经元健康之间关系的重要性。MS中的脱髓鞘导致许多病理生理变化，促成轴突生成。其中包括线粒体功能障碍，持续性神经炎症以及活性氧和氮物质的影响。有了这些信息，我们将审查目前批准的和正在研究的疗法，这些疗法旨在恢复失去或受损的髓磷脂并防止神经元变性。

概括

为了恢复MS患者的利益，开发恢复髓鞘丢失和保护神经元的疗法是一个有前途的研究途径。