| First Author | Basak JM | Year | 2012 |
| Journal | J Biol Chem | Volume | 287 |
| Issue | 17 | Pages | 13959-71 |
| PubMed ID | 22383525 | Mgi Jnum | J:241474 |
| Mgi Id | MGI:5902678 | Doi | 10.1074/jbc.M111.288746 |
| Citation | Basak JM, et al. (2012) Low-density lipoprotein receptor represents an apolipoprotein E-independent pathway of Abeta uptake and degradation by astrocytes. J Biol Chem 287(17):13959-71 |
| abstractText | Accumulation of the amyloid beta (Abeta) peptide within the brain is hypothesized to be one of the main causes underlying the pathogenic events that occur in Alzheimer disease (AD). Consequently, identifying pathways by which Abeta is cleared from the brain is crucial for better understanding of the disease pathogenesis and developing novel therapeutics. Cellular uptake and degradation by glial cells is one means by which Abeta may be cleared from the brain. In the current study, we demonstrate that modulating levels of the low-density lipoprotein receptor (LDLR), a cell surface receptor that regulates the amount of apolipoprotein E (apoE) in the brain, altered both the uptake and degradation of Abeta by astrocytes. Deletion of LDLR caused a decrease in Abeta uptake, whereas increasing LDLR levels significantly enhanced both the uptake and clearance of Abeta. Increasing LDLR levels also enhanced the cellular degradation of Abeta and facilitated the vesicular transport of Abeta to lysosomes. Despite the fact that LDLR regulated the uptake of apoE by astrocytes, we found that the effect of LDLR on Abeta uptake and clearance occurred in the absence of apoE. Finally, we provide evidence that Abeta can directly bind to LDLR, suggesting that an interaction between LDLR and Abeta could be responsible for LDLR-mediated Abeta uptake. Therefore, these results identify LDLR as a receptor that mediates Abeta uptake and clearance by astrocytes, and provide evidence that increasing glial LDLR levels may promote Abeta degradation within the brain. |
