| First Author | Lin JP | Year | 2017 |
| Journal | Elife | Volume | 6 |
| PubMed ID | 29251594 | Mgi Jnum | J:254920 |
| Mgi Id | MGI:6110896 | Doi | 10.7554/eLife.30498 |
| Citation | Lin JP, et al. (2017) LRP1 regulates peroxisome biogenesis and cholesterol homeostasis in oligodendrocytes and is required for proper CNS myelin development and repair. Elife 6:e30498 |
| abstractText | 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-gamma 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. |
