Corinne Goldsmith Dickinson Center for MS, Mount Sinai School of Medicine, New York, NY 10029, USA.
FEBS Lett. 2011 Dec 1;585(23):3813-20. doi: 10.1016/j.febslet.2011.08.017. Epub 2011 Aug 18.
Multiple sclerosis (MS) is an inflammatory demyelinating disease of the CNS. Conduction block in demyelinated axons underlies early neurological symptoms, but axonal transection and neuronal loss are believed to be responsible for more permanent chronic deficits. Several therapies are approved for treatment of relapsing-remitting MS, all of which are immunoregulatory and clinically proven to reduce the rate of lesion formation and exacerbation. However, existing approaches are only partially effective in preventing the onset of disability in MS patients, and novel treatments to protect myelin-producing oligodendrocytes and enhance myelin repair may improve long-term outcomes. Studies in vivo in genetically modified mice have assisted in the characterization of mechanisms underlying the generation of neuropathology in MS patients, and have identified potential avenues for oligodendrocyte protection and myelin repair. However, no treatments are yet approved that target these areas directly, and in addition, the relationship between demyelination and axonal transection in the lesions of the disease remains unclear. Here, we review translational research targeting oligodendrocyte protection and myelin repair in models of autoimmune demyelination, and their potential relevance as therapies in MS.
多发性硬化症（MS）是一种中枢神经系统的炎症性脱髓鞘疾病。脱髓鞘轴突中的传导阻滞是早期神经症状的基础，但轴突横断和神经元丢失被认为是导致更持久的慢性缺陷的原因。有几种疗法被批准用于治疗复发缓解型多发性硬化症，所有这些疗法都是免疫调节的，并且已被临床证明可降低病变形成和恶化的速度。然而，现有的方法在预防多发性硬化症患者残疾的发生方面仅部分有效，保护髓鞘生成少突胶质细胞和增强髓鞘修复的新疗法可能会改善长期预后。在基因修饰小鼠中的体内研究有助于阐明 MS 患者神经病理学产生的机制，并确定了少突胶质细胞保护和髓鞘修复的潜在途径。然而，目前还没有批准任何直接针对这些领域的治疗方法，此外，疾病病变中脱髓鞘与轴突横断之间的关系仍不清楚。在这里，我们综述了针对自身免疫性脱髓鞘模型中的少突胶质细胞保护和髓鞘修复的转化研究，以及它们作为多发性硬化症治疗方法的潜在相关性。
