生物
调节器
转录因子
髓鞘碱性蛋白
奥利格2
多发性硬化
神经科学
轴突
再生(生物学)
作者
Jianqin Niu,Guangdan Yu,Xiaorui Wang,Wenlong Xia,Yuxin Wang,Kimberly K. Hoi,Feng Mei,Lan Xiao,Jonah R. Chan,Stephen P.J. Fancy
出处
期刊:Neuron
[Elsevier]
日期:2021-10-06
卷期号:109 (19)
被引量:2
标识
DOI:10.1016/j.neuron.2021.07.018
摘要
Summary Oligodendrocyte (OL) maturation arrest in human white matter injury contributes significantly to the failure of endogenous remyelination in multiple sclerosis (MS) and newborn brain injuries such as hypoxic ischemic encephalopathy (HIE) that cause cerebral palsy. In this study, we identify an oligodendroglial-intrinsic factor that controls OL maturation specifically in the setting of injury. We find a requirement for the ring finger protein Rnf43 not in normal development but in neonatal hypoxic injury and remyelination in the adult mammalian CNS. Rnf43, but not the related Znrf3, is potently activated by Wnt signaling in OL progenitor cells (OPCs) and marks activated OPCs in human MS and HIE. Rnf43 is required in an injury-specific context, and it promotes OPC differentiation through negative regulation of Wnt signal strength in OPCs at the level of Fzd1 receptor presentation on the cell surface. Inhibition of Fzd1 using UM206 promotes remyelination following ex vivo and in vivo demyelinating injury.
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