Gallo Vittorio, Armstrong Regina C
Center for Neuroscience Research, Children's National Medical Center, Washington, District of Columbia 20010, USA.
Curr Opin Neurol. 2008 Jun;21(3):278-83. doi: 10.1097/WCO.0b013e3282fd1875.
The development of successful myelin repair strategies depends on the detailed knowledge of the cellular and molecular processes underlying demyelination and remyelination in the central nervous system of animal models and in patients with multiple sclerosis (MS). Based on the complexity of the demyelination and remyelination processes, it should be expected that effective therapeutic approaches will require a combination of strategies for immunomodulation, neuroprotection, and myelin replacement. This brief review highlights recent cellular and molecular findings and indicates that future therapeutic strategies to enhance remyelination may also require combinatorial treatment to accomplish.
The relapsing-remitting course of some forms of multiple sclerosis has typically fueled hope for effective repair of multiple sclerosis lesions, if demyelinating activity could be attenuated. Recent findings support the potential of endogenous neural stem cells and progenitor cells to generate remyelinating oligodendrocytes. Importantly, interactions with viable axons and supportive astrocytic responses are required for endogenous immature cells to fulfill their potential remyelinating capacity.
The research described here will help in identifying the major obstacles to effective remyelination and potential therapeutic targets to guide development of comprehensive approaches for testing in animal models and eventual treatment of patients with multiple sclerosis.
成功的髓鞘修复策略的发展取决于对动物模型和多发性硬化症(MS)患者中枢神经系统中脱髓鞘和髓鞘再生潜在的细胞和分子过程的详细了解。基于脱髓鞘和髓鞘再生过程的复杂性,可以预期有效的治疗方法将需要免疫调节、神经保护和髓鞘替代策略的组合。本简要综述重点介绍了最近的细胞和分子研究结果,并表明未来增强髓鞘再生的治疗策略可能也需要联合治疗才能实现。
如果能够减弱脱髓鞘活动,某些形式的多发性硬化症的复发缓解病程通常会燃起有效修复多发性硬化症病变的希望。最近的研究结果支持内源性神经干细胞和祖细胞生成髓鞘再生少突胶质细胞的潜力。重要的是,内源性未成熟细胞要发挥其潜在的髓鞘再生能力,需要与存活的轴突相互作用以及星形胶质细胞的支持性反应。
这里描述的研究将有助于确定有效髓鞘再生的主要障碍以及潜在的治疗靶点,以指导开发在动物模型中进行测试并最终治疗多发性硬化症患者的综合方法。