Could the inhibitor of DNA binding 2 and 4 play a role in white matter injury?

Xiaoyun Gou, Ying Tang, Yi Qu, Dongqiong Xiao, Junjie Ying, Dezhi Mu

Reviews in the neurosciences 2019 Jul 26

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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.

Citation

Xiaoyun Gou, Ying Tang, Yi Qu, Dongqiong Xiao, Junjie Ying, Dezhi Mu. Could the inhibitor of DNA binding 2 and 4 play a role in white matter injury? Reviews in the neurosciences. 2019 Jul 26;30(6):625-638