Figure 1.

apoE and cholesterol transport and efflux. (A) In astrocytes, cholesterol synthesis is regulated by the liver X receptors (LXRs) and the retinoid X receptor (RXR). The LXR/RXR heterodimer interacts with sequence-specific DNA elements positioned close to enhancers or promoters of their target genes, including the ABCA1, ABCG1, and APOE, thus acting directly to upregulate their transcription. (B) apoE initiates the formation of high-density lipoprotein (HDL)-like particles by accepting cholesterol and phospholipids through the ABCA1 and ABCG1 transporters. (C) apoE-containing lipoproteins and lipid complexes interact with cell surface heparin sulfate proteoglycans and cell membrane associated receptors, including the LDL receptor and the LDL receptor-related protein 1 (LRP) in neurons. This interaction promotes cellular uptake and redistribution of cholesterol to maintain proper cellular function, including neuronal growth, repair and remodeling of membranes, organelle biogenesis, and synaptogenesis.