@article{6f8333a5354c4d6abcfebaab2844fedc,
title = "LRP1 regulates peroxisome biogenesis and cholesterol homeostasis in oligodendrocytes and is required for proper CNS myelin development and repair",
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-g 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.",
author = "Lin, {Jing Ping} and Mironova, {Yevgeniya A.} and Peter Shrager and Giger, {Roman J.}",
note = "Funding Information: We thank Andy Lieberman for providing CAG-CreERTM mice, Ben Barres for providing Olig2-Cre mice, and Richard Lu for Plp1 plasmid DNA. We thank Chang-Ting Lin, Wei-Chin Ho, and Chih-Hsu Lin for bioinformatics consulting. This work was supported by a Bradley Merrill Patten Fellowship (J- PL), the Training Program in Organogenesis T32HD007505 and NIH Cellular and Molecular Biology Training Grant T32-GM007315 (YAM), R01 NS081281 (PS and RJG), the Schmitt Program on Integrative Brain Research (PS), and the Dr. Miriam and Sheldon G. Adelson Medical Foundation on Neural Repair and Rehabilitation (RJG). Eunice Kennedy Shriver National Institute of Child Health and Human Development T32HD007505 Yevgeniya A Mironova National Institute of General Medical Sciences T32GM007315 Yevgeniya A Mironova National Institute of Neurological Disorders and Stroke R01NS081281 Peter Shrager Roman J Giger\ Schmitt Program on Integrative Brain Research Peter Shrager Dr. Miriam and Sheldon G. Adelson Medical Research Foundation APNRR Roman J Giger Bradley Merrill Patten Fellowship Jing-Ping Lin The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication. Funding Information: We thank Andy Lieberman for providing CAG-CreERTM mice, Ben Barres for providing Olig2-Cre mice, and Richard Lu for Plp1 plasmid DNA. We thank Chang-Ting Lin, Wei-Chin Ho, and Chih-Hsu Lin for bioinformatics consulting. This work was supported by a Bradley Merrill Patten Fellowship (J-PL), the Training Program in Organogenesis T32HD007505 and NIH Cellular and Molecular Biology Training Grant T32-GM007315 (YAM), R01 NS081281 (PS and RJG), the Schmitt Program on Integrative Brain Research (PS), and the Dr. Miriam and Sheldon G. Adelson Medical Foundation on Neural Repair and Rehabilitation (RJG). Publisher Copyright: {\textcopyright} Lin et al.",
year = "2017",
month = dec,
day = "18",
doi = "10.7554/eLife.30498",
language = "English (US)",
volume = "6",
journal = "eLife",
issn = "2050-084X",
publisher = "eLife Sciences Publications",
}