| Literature DB >> 34610310 |
Yan Wang1, Yanhong Zhang1, Sheng Zhang1, Bokyung Kim1, Vanessa L Hull1, Jie Xu2, Preeti Prabhu1, Maria Gregory1, Veronica Martinez-Cerdeno3, Xinhua Zhan4, Wenbin Deng5, Fuzheng Guo6.
Abstract
The function of poly(ADP-ribosyl) polymerase 1 (PARP1) in myelination and remyelination of the central nervous system (CNS) remains enigmatic. Here, we report that PARP1 is an intrinsic driver for oligodendroglial development and myelination. Genetic PARP1 depletion impairs the differentiation of oligodendrocyte progenitor cells (OPCs) into oligodendrocytes and impedes CNS myelination. Mechanistically, PARP1-mediated PARylation activity is not only necessary but also sufficient for OPC differentiation. At the molecular level, we identify the RNA-binding protein Myef2 as a PARylated target, which controls OPC differentiation through the PARylation-modulated derepression of myelin protein expression. Furthermore, PARP1's enzymatic activity is necessary for oligodendrocyte and myelin regeneration after demyelination. Together, our findings suggest that PARP1-mediated PARylation activity may be a potential therapeutic target for promoting OPC differentiation and remyelination in neurological disorders characterized by arrested OPC differentiation and remyelination failure such as multiple sclerosis.Entities:
Keywords: OPC differentiation; PARG; PARP1; PARylation; demyelination; multiple sclerosis; myelination; oligodendrocyte progenitor cells (OPCs); oligodendrocytes (OLs); remyelination
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Year: 2021 PMID： 34610310 PMCID： PMC9586836 DOI： 10.1016/j.celrep.2021.109695
Source DB: PubMed Journal: Cell Rep Impact factor: 9.995