The biology of CNS remyelination - The key to therapeutic advances
The biology of CNS remyelination - The key to therapeutic advances
复制标题
DOI：
10.1007/s00415-008-1004-6
复制
发表时间：
2008-03-01
影响因子：
6
通讯作者：
Kotter, Mark R.
中科院分区：
文献类型：
--
作者：
Franklin, Robin J. M.;Kotter, Mark R.
再髓鞘形成是新髓鞘恢复为脱髓鞘轴突的过程，是成体多能祖细胞促进受损CNS再生的最引人注目的例子之一。这一过程在临床疾病（如多发性硬化症）和实验模型中都能以显著的效率发生，揭示了成人CNS自我修复的惊人能力。然而，在多发性硬化症中髓鞘再生的不一致性，以及由其失败导致的轴突完整性的丧失，使得髓鞘再生的增强成为重要的治疗目标。确定潜在的目标需要详细了解髓鞘再生的细胞和分子机制。实现有效髓鞘再生的关键步骤是前体细胞分化为成熟的少突胶质细胞。在老年动物脱髓鞘疾病以及多发性硬化症的实验模型中，这种分化似乎受到了损害。这至少部分是由于控制髓鞘再生的环境信号的变化。特别是，损伤内的髓鞘碎片似乎含有前体细胞分化的强大抑制剂。因此，通过巨噬细胞有效去除髓鞘碎片可以促进分化并允许受损轴突的成功髓鞘再生。这可能代表了一个有前途的治疗目标，促进髓鞘再生多发性硬化症，从而限制不可逆的神经功能障碍的积累。
Remyelination, the process by which new myelin sheaths are restored to demyelinated axons, represents one of the most compelling examples of adult multipotent progenitor cells contributing to regeneration of the injured CNS. This process can occur with remarkable efficiency in both clinical disease, such as multiple sclerosis, and in experimental models, revealing an impressive ability of the adult CNS to repair itself. However, the inconsistency of remyelination in multiple sclerosis, and the loss of axonal integrity that results from its failure, makes enhancement of remyelination an important therapeutic objective. Identifying potential targets requires a detailed understanding of the cellular and molecular mechanisms of remyelination. A critical step in achieving effective remyelination is the differentiation of precursor cells into mature oligodendrocytes. In experimental models of demyelinating disease in aged animals, as well as in multiple sclerosis, such differentiation appears to be impaired. This is due, at least in part, to changes in environmental signals governing remyelination. In particular, myelin debris within lesions appears to contain powerful inhibitors of precursor cell differentiation. Efficient removal of myelin debris by macrophages may thus facilitate differentiation and permit successful remyelination of damaged axons. This may represent a promising therapeutic target for promoting remyelination in multiple sclerosis and thus limiting the accumulation of irreversible neurological disability.