LRP1 regulates peroxisome biogenesis and cholesterol homeostasis in oligodendrocytes and is required for proper CNS myelin development and repair

Low-density lipoprotein receptor-related protein-1 (LRP1) is a large endocytic and signaling molecule broadly expressed by neurons and glia. In adult mice, global inducible ( ) or oligodendrocyte (OL)-lineage specific ablation ( ) of attenuates repair of damaged white matter. In oligodendrocyte prog...

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Bibliographic Details
Published in:eLife 2017-12, Vol.6
Main Authors: Lin, Jing-Ping, Mironova, Yevgeniya A, Shrager, Peter, Giger, Roman J
Format: Article
Language:English
Subjects:
Ablation
Biosynthesis
Central nervous system
Cholesterol
Cholesterol Homeostasis
CNS Myelin Repair
Gene expression
Glial stem cells
Homeostasis
Labeling
Ligands
Low density lipoproteins
LRP1
Medical research
mouse
Myelin
Neomycin
Neuronal-glial interactions
Neurons
Neuroscience
Neurosciences
Novels
Oligodendrocyte differentiation
Oligodendrocytes
Ontology
Peroxisome Biogenesis
Peroxisome proliferator-activated receptors
Peroxisomes
Pioglitazone
Platelet-derived growth factor
Progenitor cells
Protein binding
Proteins
Receptor density
Signal transduction
Software
Substantia alba
Trinucleotide repeats
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Summary:Low-density lipoprotein receptor-related protein-1 (LRP1) is a large endocytic and signaling molecule broadly expressed by neurons and glia. In adult mice, global inducible ( ) or oligodendrocyte (OL)-lineage specific ablation ( ) of attenuates repair of damaged white matter. In oligodendrocyte progenitor cells (OPCs), is required for cholesterol homeostasis and differentiation into mature OLs. deficient OPC/OLs show a strong increase in the sterol-regulatory element-binding protein-2 yet are unable to maintain normal cholesterol levels, suggesting more global metabolic deficits. Mechanistic studies revealed a decrease in peroxisomal biogenesis factor-2 and fewer peroxisomes in OL processes. Treatment of OPCs with cholesterol or activation of peroxisome proliferator-activated receptor-γ with pioglitazone alone is not sufficient to promote differentiation; however, when combined, cholesterol and pioglitazone enhance OPC differentiation into mature OLs. Collectively, our studies reveal a novel role for in peroxisome biogenesis, lipid homeostasis, and OPC differentiation during white matter development and repair.
ISSN:2050-084X
2050-084X
DOI:10.7554/eLife.30498