During demyelinating disease such as multiple sclerosis and stroke, myelin is destroyed and along with it, the oligodendrocytes that synthesize the myelin. Thus, recovery is limited due to both interruptions in neuronal transmission as well as lack of support for neurons. Although oligodendrocyte progenitor cells remain abundant in the central nervous system, they rarely mature and form new functional myelin in the diseased CNS. In cell culture and in experimental models of demyelinating disease, inhibitory signaling factors decrease myelination and remyelination. One of the most potent of these are the bone morphogenetic proteins (BMPs), a family of proteins that strongly inhibits oligodendrocyte progenitor differentiation and myelination in culture. BMPs are highly expressed in the dorsal CNS during pre-natal development and serve to regulate dorsal ventral patterning. Their expression decreases after birth but is significantly increased in rodent demyelination models such as experimental autoimmune encephalomyelitis, cuprizone ingestion and spinal cord injury. However, until recently, evidence for BMP upregulation in human disease has been scarce. This review discusses new human studies showing that in multiple sclerosis and other demyelinating diseases, BMPs are expressed by immune cells invading the CNS as well as resident CNS cell types, mostly astrocytes and microglia. Expression of endogenous BMP antagonists is also regulated. Identification of BMPs in the CNS is correlated with areas of demyelination and inflammation. These studies further support BMP as a potential therapeutic target.

中文翻译：

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髓鞘形成和再髓鞘形成的抑制剂，骨形态发生蛋白，在人类神经系统疾病中被上调。

在多发性硬化症和中风等脱髓鞘疾病期间，髓磷脂被破坏，合成髓鞘的少突胶质细胞也随之被破坏。因此，由于神经元传递的中断以及缺乏对神经元的支持，恢复受到限制。尽管少突胶质细胞祖细胞在中枢神经系统中仍然丰富，但它们很少成熟并在患病的中枢神经系统中形成新的功能性髓磷脂。在细胞培养和脱髓鞘疾病的实验模型中，抑制性信号转导因子降低了髓鞘形成和髓鞘再生。其中最有效的一种是骨形态发生蛋白（BMP），这是一种蛋白家族，可强烈抑制培养中少突胶质细胞祖细胞的分化和髓鞘形成。BMP在产前发育期间在背侧CNS中高度表达，并用于调节背侧腹侧结构。它们的表达在出生后会降低，但在啮齿动物脱髓鞘模型（例如实验性自身免疫性脑脊髓炎，铜酮摄入和脊髓损伤）中会显着增加。但是，直到最近，人类疾病中BMP上调的证据仍然很少。这篇综述讨论了新的人类研究，这些研究表明，在多发性硬化症和其他脱髓鞘疾病中，BMPs通过侵袭CNS以及固有CNS细胞类型（主要是星形胶质细胞和小胶质细胞）的免疫细胞表达。内源性BMP拮抗剂的表达也受到调节​​。中枢神经系统中BMP的鉴定与脱髓鞘和炎症区域相关。这些研究进一步支持BMP作为潜在的治疗靶标。