Low-density lipoprotein receptor (LDLR) and Low-density lipoprotein receptor-related protein 1 (LRP1) (LDLR/LRP1)

Hepatic ApoE receptors, primarily the Low-Density Lipoprotein Receptor (LDLR) and Low-Density Lipoprotein Receptor-Related Protein 1 (LRP1), are transmembrane proteins essential for maintaining systemic lipid homeostasis (UniProt P01130, Q07954). These receptors are expressed on the surface of hepatocytes where they recognize and bind to Apolipoprotein E (ApoE) and Apolipoprotein B-100 on circulating lipoproteins, such as LDL and VLDL remnants, leading to their internalization and degradation (PubMed: 21148477). The therapeutic strategy involving ApoE-mimetic presentation utilizes synthetic peptides derived from the receptor-binding domain of natural ApoE to decorate lipoprotein particles. By associating with the surface of LDL or VLDL, these mimetics provide a high-affinity ligand that triggers receptor-mediated uptake, effectively bypassing defective endogenous clearance pathways (PubMed: 11264358). This mechanism is particularly relevant for treating severe dyslipidemias and atherosclerosis by accelerating the removal of pro-atherogenic lipids from the blood. Drugs targeting this pathway, such as AEM-28, offer a promising alternative for patients with refractory hypercholesterolemia who do not respond adequately to traditional statin therapy.

Other names

LDLRLRP1CD91Apolipoprotein E receptorApoE receptorHepatic lipoprotein receptorsLow-density lipoprotein receptor-related protein 1

Enhancement of receptor-mediated endocytosis of lipoproteins via synthetic ligand presentation