دورية أكاديمية
أعرض في EDS

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

التفاصيل البيبلوغرافية
العنوان: LRP1 regulates peroxisome biogenesis and cholesterol homeostasis in oligodendrocytes and is required for proper CNS myelin development and repair.
المؤلفون: Lin JP; Department of Cell and Developmental Biology, University of Michigan School of Medicine, Ann Arbor, MI, United States., Mironova YA; Cellular and Molecular Biology Graduate Program, University of Michigan Medical School, Ann Arbor, MI, United States., Shrager P; Department of Neuroscience, University of Rochester Medical Center, Rochester, NY, United States., Giger RJ; Department of Cell and Developmental Biology, University of Michigan School of Medicine, Ann Arbor, MI, United States.; Cellular and Molecular Biology Graduate Program, University of Michigan Medical School, Ann Arbor, MI, United States.; Department of Neurology, University of Michigan Medical School, Ann Arbor, MI, United States.; Interdepartmental Neuroscience Graduate Program, University of Michigan Medical School, Ann Arbor, MI, United States.
المصدر: ELife [Elife] 2017 Dec 18; Vol. 6. Date of Electronic Publication: 2017 Dec 18.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: eLife Sciences Publications, Ltd Country of Publication: England NLM ID: 101579614 Publication Model: Electronic Cited Medium: Internet ISSN: 2050-084X (Electronic) Linking ISSN: 2050084X NLM ISO Abbreviation: Elife Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Cambridge, UK : eLife Sciences Publications, Ltd., 2012-
مواضيع طبية MeSH: Homeostasis* , Organelle Biogenesis*, Cholesterol/*metabolism , Myelin Sheath/*metabolism , Oligodendrocyte Precursor Cells/*physiology , Peroxisomes/*metabolism , Receptors, LDL/*metabolism , Tumor Suppressor Proteins/*metabolism, Animals ; Cell Differentiation ; Cells, Cultured ; Low Density Lipoprotein Receptor-Related Protein-1 ; Mice
مستخلص: 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 ( Lrp1 flox/flox ;CAG-CreER ) or oligodendrocyte (OL)-lineage specific ablation ( Lrp1 flox/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.
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معلومات مُعتمدة: R01 NS081281 United States NS NINDS NIH HHS; T32 GM007315 United States GM NIGMS NIH HHS; T32 HD007505 United States HD NICHD NIH HHS
فهرسة مساهمة: Keywords: CNS Myelin Repair; Cholesterol Homeostasis; LRP1; Oligodendrocyte differentiation; Peroxisome Biogenesis; mouse; neuroscience
المشرفين على المادة: 0 (Low Density Lipoprotein Receptor-Related Protein-1)
0 (Lrp1 protein, mouse)
0 (Receptors, LDL)
0 (Tumor Suppressor Proteins)
97C5T2UQ7J (Cholesterol)
تواريخ الأحداث: Date Created: 20171219 Date Completed: 20180822 Latest Revision: 20201209
رمز التحديث: 20221213
مُعرف محوري في PubMed: PMC5752207
DOI: 10.7554/eLife.30498
PMID: 29251594
قاعدة البيانات: MEDLINE
الوصف
تدمد:2050-084X
DOI:10.7554/eLife.30498