White matter injury (WMI) prevents the normal development of myelination, leading to central nervous system myelination disorders and the production of chronic sequelae associated with WMI, such as chronic dyskinesia, cognitive impairment and cerebral palsy. This results in a large emotional and socioeconomic burden. Decreased myelination in preterm infant WMI is associated with the delayed development or destruction of oligodendrocyte (OL) lineage cells, particularly oligodendrocyte precursor cells (OPCs). The development of cells from the OL lineage involves the migration, proliferation and different stages of OL differentiation, finally leading to myelination. A series of complex intrinsic, extrinsic and epigenetic factors regulate the OPC cell cycle withdrawal, OL lineage progression and myelination. We focus on the inhibitor of DNA binding 2 (ID2), because it is widely involved in the different stages of OL differentiation and genesis. ID2 is a key transcription factor for the normal development of OL lineage cells, and the pathogenesis of WMI is closely linked with OL developmental disorders. ID4, another family member of the IDs protein, also plays a similar role in OL differentiation and genesis. ID2 and ID4 belong to the helix-loop-helix family; they lack the DNA-binding sequences and inhibit oligodendrogenesis and OPC differentiation. In this review, we mainly discuss the roles of ID2 in OL development, especially during OPC differentiation, and summarize the ID2-mediated intracellular and extracellular signaling pathways that regulate these processes. We also discuss ID4 in relation to bone morphogenetic protein signaling and oligodendrogenesis. It is likely that these developmental mechanisms are also involved in the myelin repair or remyelination in human neurological diseases.

中文翻译：

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DNA结合2和4的抑制剂会在白质损伤中起作用吗？

白质损伤 (WMI) 阻止髓鞘形成的正常发育，导致中枢神经系统髓鞘形成障碍和与 WMI 相关的慢性后遗症的产生，例如慢性运动障碍、认知障碍和脑瘫。这导致了巨大的情感和社会经济负担。早产儿 WMI 髓鞘形成减少与少突胶质细胞 (OL) 谱系细胞，尤其是少突胶质前体细胞 (OPCs) 的发育延迟或破坏有关。OL 谱系细胞的发育涉及 OL 分化的迁移、增殖和不同阶段，最终导致髓鞘形成。一系列复杂的内在、外在和表观遗传因素调节 OPC 细胞周期停止、OL 谱系进展和髓鞘形成。我们专注于 DNA 结合 2 (ID2) 的抑制剂，因为它广泛参与 OL 分化和发生的不同阶段。ID2是OL谱系细胞正常发育的关键转录因子，WMI的发病机制与OL发育障碍密切相关。ID4 是 IDs 蛋白的另一个家族成员，在 OL 的分化和发生中也起着类似的作用。ID2 和 ID4 属于 helix-loop-helix 家族；它们缺乏 DNA 结合序列并抑制少突胶质细胞生成和 OPC 分化。在这篇综述中，我们主要讨论了 ID2 在 OL 发育中的作用，特别是在 OPC 分化过程中，并总结了 ID2 介导的调节这些过程的细胞内和细胞外信号通路。我们还讨论了 ID4 与骨形态发生蛋白信号传导和少突形成的关系。这些发育机制很可能也参与了人类神经系统疾病的髓鞘修复或髓鞘再生。