Blocking CK2α ‐Bclaf1 Preserves Oligodendrocytes After Neonatal Hypoxic Injury

ABSTRACT

Neonatal hypoxic injury is a common disorder that disrupts white matter development in preterm newborns, with long‐term impacts on cognitive and mental function. While oxygen availability controls oligodendrocyte (OL) differentiation, prolonged hypoxia leads to OL death and impairs subsequent myelination even after returning to normoxic conditions. In this study, we uncovered the detrimental roles of the serine/threonine kinase CK2α and the transcriptional factor Bclaf1 in OL survival under hypoxic conditions. Phosphorylated Bclaf1 by CK2α drives hypoxia‐mediated OL apoptosis, which can be reversed by introducing the hypoxia‐inducible E3 ligase Vhl. Additionally, acute treatment with the clinically approved CK2 inhibitor silmitasertib and the herbal supplement curcumin not only reduces CK2α‐Bclaf1 activity but also protects OLs and restores pre‐myelinating ability in newborns following hypoxic injury. This approach unveils a key molecular regulation in hypoxia‐related OL pathology and highlights a potential therapeutic strategy to mitigate neonatal hypoxic injury and prevent mental health complications.