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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.
Pubmed ID: 29251594 RIS Download
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View all literature mentionsMus musculus with name C57BL/6J from IMSR.
View all literature mentionsThis polyclonal targets Oligodendrocute transcription factor 2
View all literature mentionsThis polyclonal targets NG2 Chondroitin Sulfate Proteoglycan
View all literature mentionsThis monoclonal targets Cnp
View all literature mentionsThis polyclonal targets Myelin PLP antibody
View all literature mentionsThis monoclonal targets slightly modified β-cytoplasmic actin N-terminal peptide, Ac-Asp-Asp-Asp-Ile-Ala-Ala-Leu-Val-Ile-Asp-Asn-Gly-Ser-Gly-Lys, conjugated to KLH
View all literature mentionsThis monoclonal targets βIII Tubulin
View all literature mentionsThis unknown targets PMP70
View all literature mentionsThis monoclonal targets LRP1
View all literature mentionsThis monoclonal targets GFAP
View all literature mentionsThis monoclonal targets Myelin Basic Protein (MBP), aa 82-87
View all literature mentionsThis polyclonal targets Contactin-associated protein (Caspr)
View all literature mentionsThis monoclonal targets APC
View all literature mentionsThis polyclonal targets Rabbit Glial Fibrillary Acidic Protein (GFAP)
View all literature mentionsThis monoclonal targets CD140a
View all literature mentionsMus musculus with name B6N.Cg-Tg(Pdgfra-cre/ERT)467Dbe/J from IMSR.
View all literature mentionsMus musculus with name B6.Cg-Tg(CAG-cre/Esr1*)5Amc/J from IMSR.
View all literature mentionsMus musculus with name STOCK Tg(Odc1-EGFP)EI44Gsat/Mmucd from MMRRC.
View all literature mentionsMus musculus with name B6;129S7-Lrp1tm2Her/J from IMSR.
View all literature mentionsThis monoclonal targets Cnp
View all literature mentionsThis polyclonal targets Myelin PLP antibody
View all literature mentionsThis monoclonal targets slightly modified β-cytoplasmic actin N-terminal peptide, Ac-Asp-Asp-Asp-Ile-Ala-Ala-Leu-Val-Ile-Asp-Asn-Gly-Ser-Gly-Lys, conjugated to KLH
View all literature mentionsThis monoclonal targets βIII Tubulin
View all literature mentionsThis unknown targets PMP70
View all literature mentionsThis monoclonal targets LRP1
View all literature mentionsThis monoclonal targets GFAP
View all literature mentionsThis monoclonal targets Myelin Basic Protein (MBP), aa 82-87
View all literature mentionsThis polyclonal targets Contactin-associated protein (Caspr)
View all literature mentionsThis monoclonal targets APC
View all literature mentionsThis polyclonal targets Rabbit Glial Fibrillary Acidic Protein (GFAP)
View all literature mentionsThis monoclonal targets CD140a
View all literature mentionsMus musculus with name B6N.Cg-Tg(Pdgfra-cre/ERT)467Dbe/J from IMSR.
View all literature mentionsMus musculus with name B6.Cg-Tg(CAG-cre/Esr1*)5Amc/J from IMSR.
View all literature mentionsMus musculus with name STOCK Tg(Odc1-EGFP)EI44Gsat/Mmucd from MMRRC.
View all literature mentionsMus musculus with name B6;129S7-Lrp1tm2Her/J from IMSR.
View all literature mentionsThis polyclonal targets Oligodendrocute transcription factor 2
View all literature mentionsThis polyclonal targets NG2 Chondroitin Sulfate Proteoglycan
View all literature mentionsThis polyclonal targets NG2 Chondroitin Sulfate Proteoglycan
View all literature mentionsThis polyclonal targets Oligodendrocute transcription factor 2
View all literature mentionsThis polyclonal targets NG2 Chondroitin Sulfate Proteoglycan
View all literature mentionsThis polyclonal targets Oligodendrocute transcription factor 2
View all literature mentionsThis polyclonal targets NG2 Chondroitin Sulfate Proteoglycan
View all literature mentionsThis polyclonal targets Oligodendrocute transcription factor 2
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