PARP1-mediated PARylation activity is essential for oligodendroglial differentiation and CNS myelination

Autor: Vanessa Hull, Sheng Zhang, Maria Gregory, Preeti Prabhu, Yan Wang, Bokyung Kim, Verónica Martínez-Cerdeño, Xinhua Zhan, Wenbin Deng, Jie Xu, Yanhong Zhang, Fuzheng Guo
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Central Nervous System
Male
Medical Physiology
Poly (ADP-Ribose) Polymerase-1
Neurodegenerative
Inbred C57BL
Regenerative Medicine
PARP1
Mice
Poly ADP Ribosylation
Myelin
Biology (General)
Myelin Sheath
Derepression
Mice
Knockout
oligodendrocyte progenitor cells
myelination
Cell Differentiation
Cell biology
Oligodendroglia
medicine.anatomical_structure
oligodendrocytes (OLs)
Neurological
Female
Stem Cell Research - Nonembryonic - Non-Human
demyelination
OPC differentiation
Multiple Sclerosis
Cell Survival
QH301-705.5
Knockout
1.1 Normal biological development and functioning
Central nervous system
oligodendrocytes
Nerve Tissue Proteins
Biology
Autoimmune Disease
General Biochemistry
Genetics and Molecular Biology
Cuprizone
Underpinning research
medicine
Animals
PARG
Remyelination
Oligodendrocyte Precursor Cells
Multiple sclerosis
Regeneration (biology)
Neurosciences
Oligodendrocyte Transcription Factor 2
Stem Cell Research
medicine.disease
Oligodendrocyte
Brain Disorders
Mice
Inbred C57BL
Repressor Proteins
PARylation
stomatognathic diseases
remyelination
nervous system
RNA
oligodendrocyte progenitor cells (OPCs)
Biochemistry and Cell Biology
Zdroj: Cell Reports, Vol 37, Iss 1, Pp 109695-(2021)
Cell reports, vol 37, iss 1
ISSN: 2211-1247
Popis: Summary: 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.
Databáze: OpenAIRE
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