Low-density lipoprotein receptor-related protein 1 (LRP1) (LRP1)

Low-density lipoprotein receptor-related protein 1 (LRP1), also known as CD91, is a large, multifunctional endocytic receptor belonging to the LDL receptor family (UniProt Q07954). The CR6-7 doublet refers to a specific structural unit consisting of the sixth and seventh complement-type repeats within the Cluster II ligand-binding domain of the LRP1 alpha-chain (Jensen et al., 2000, J. Biol. Chem.). This specific doublet is a critical binding site for several ligands, most notably alpha-2-macroglobulin and apolipoprotein E, and is essential for their internalization and clearance (PubMed 11032761). LRP1 is highly expressed on the blood-brain barrier (BBB), where it facilitates the transport of ligands from the blood into the brain parenchyma via receptor-mediated transcytosis (PubMed 18474911). This property has made the LRP1 CR6-7 region a primary target for drug delivery systems, such as Angiopep-2 (ANG1005), which are designed to bypass the BBB to treat central nervous system disorders like brain metastases (Demeule et al., 2008, J. Pharmacol. Exp. Ther.). Beyond drug delivery, LRP1 is heavily implicated in the clearance of amyloid-beta in Alzheimer's disease and the regulation of inflammatory responses in atherosclerosis (PubMed 22048246).

Other names

CD91Alpha-2-macroglobulin receptorA2MRApolipoprotein E receptorAPOERLRP1 Cluster IILRP1 CR6-7

Receptor-mediated transcytosis and endocytosis for ligand clearance and drug delivery