Apolipoprotein E (“ApoE”) is a 299 amino acid (34 kDa) glycoprotein, produced primarily in the liver and brain that exhibits multiple biological functions. First recognized for its role in cholesterol transport and metabolism, ApoE is present in very-low-density lipoprotein (VLDL) and high-density lipoprotein (HDL) complexes, and ApoE can bind the low-density lipoprotein (LDL) receptor, the LDL-receptor-related protein (LRP), and the VLDL receptor. Weisgraber, (1994) Adv. Protein Chem. 45:249-302. ApoE is also known to have immunomodulatory properties, Laskowitz, et al., (2001) Exp. Neurol. 167:74-85, and to play a role in neurological disease and brain injury response, Laskowitz and Vitek, (2007) Pharmacogenomics 8:959-69.
The tertiary structure of ApoE includes an amino-terminal region with a four-α-helix motif that includes a receptor-binding domain and a carboxy-terminal region that is largely responsible for lipid binding. The receptor-binding region of ApoE has been mapped to a helical domain at residues 130-150 of the mature full-length protein, and this region of ApoE governs its ability to suppress glial activation and CNS inflammation.
USPTO Backgrounds
USPTO Backgrounds