Modulating Glial Fate and Function in Development and Disease

摘要 人类中枢神经系统中的1000亿个神经元中的许多需要具有保护性和绝缘的 被称为髓鞘的涂层才能正常发挥作用。这种髓鞘涂层的丢失或损伤是许多神经系统疾病的基础 疾病和新髓鞘的再生是改善患者健康的重要部分 多发性硬化症(MS)、视神经脊髓炎(NMO)和其他髓鞘疾病，如儿科 脑白质营养不良。如果没有髓鞘，某些神经细胞就不能正常传导电脉冲，导致 虚弱、疲劳、失明、认知衰退和身体残疾。我们开发了一部小说 再生方法为髓鞘丢失或髓鞘缺失患者寻找重要的潜在治疗方法 功能障碍是建立在我们在干细胞生物学方面的专业知识之上的。我们的总体目标是利用体外培养的小鼠 和人类干细胞平台，我们已经开发了它们来定义负责 在各种髓鞘疾病中预防髓鞘发育和功能。我们试图发现 可以调节少突胶质细胞的功能或再生的新的治疗干预措施 恢复髓鞘形成和神经功能的星形胶质细胞。对于多发性硬化症，我们已经定义了 刺激髓鞘再生和识别可逆转的有效小分子的中心机制 疾病的小鼠模型中的瘫痪。展望未来，我们寻求利用我们的创新技术和 在多发性硬化症中识别髓鞘功能障碍的疾病和背景特异性效应因子的经验 为新的治疗方法提供基础。

SUMMARY Many of the 100 billion neurons in the human central nervous system require a protective and insulating coating called myelin to function properly. Loss or damage of this myelin coating underlies many neurological disorders and therefore regeneration of new myelin is an important part of improving health for patients with multiple sclerosis (MS), neuromyelitis optica (NMO), and other myelin diseases such as the pediatric leukodystrophies. Without myelin, certain nerve cells cannot properly conduct electrical impulses, leading to weakness, fatigue, loss of vision, cognitive decline, and physical incapacity. We have developed a novel regenerative approach to identify important new potential treatments for patients with myelin loss or dysfunction that is built upon our expertise in stem cell biology. Our overall goal is to utilize the in vitro mouse and human stem cell platforms that we have developed to define the central mechanisms responsible for preventing myelin development and function across the full range of myelin disorders. We seek to discover novel therapeutic interventions that can modulate the function or regeneration of oligodendrocytes and astrocytes to restore myelination and neurological function. For multiple sclerosis, we have already defined a central mechanism to stimulate myelin regeneration and identified potent small molecules that can reverse paralysis in mouse models of disease. Moving forward, we seek to leverage our innovative technologies and experience in multiple sclerosis to identify disease- and context-specific effectors of myelin dysfunction and provide the basis for new therapies.