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- W2754257759 abstract "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 (Lrp1flox/flox;CAG-CreER) or oligodendrocyte (OL)-lineage specific ablation (Lrp1flox/flox;Pdgfra-CreER) of Lrp1 attenuates repair of damaged white matter. In oligodendrocyte progenitor cells (OPCs), Lrp1 is required for cholesterol homeostasis and differentiation into mature OLs. Lrp1-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 Lrp1−/− 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 Lrp1 in peroxisome biogenesis, lipid homeostasis, and OPC differentiation during white matter development and repair." @default.
- W2754257759 created "2017-09-25" @default.
- W2754257759 creator A5027859811 @default.
- W2754257759 creator A5033411024 @default.
- W2754257759 creator A5039727184 @default.
- W2754257759 creator A5082719482 @default.
- W2754257759 date "2017-12-18" @default.
- W2754257759 modified "2023-09-24" @default.
- W2754257759 title "LRP1 regulates peroxisome biogenesis and cholesterol homeostasis in oligodendrocytes and is required for proper CNS myelin development and repair" @default.
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- W2754257759 doi "https://doi.org/10.7554/elife.30498" @default.
- W2754257759 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/5752207" @default.