APOE2: protective mechanism and therapeutic implications for Alzheimer’s disease

摘要

Human APOE. a Human APOE is an O-linked glycoprotein consisting of 299 amino acids. The N-terminal domain (residues 1-167) and the C-terminal domain (residues 206-299) are linked by a flexible hinge region. The receptor binding site (residues 136-150) on the N-terminus overlaps with the heparin binding region (residues 136-147). A second heparin-binding site on the C-terminal domain adjacent to the lipid binding site (residue 244-272) requires K233. Amino acid substitutions at position 112 and 158 result in the three major isoforms: APOE2 (Cys112; Cys158), APOE3 (Cys112; Arg158) and APOE4 (Arg158; Arg158). APOE has other less common isoforms; APOE (V236E) and APOE3 Christchurch (R136S) (blue triangles) are two examples that have also been suggested to protect against AD. b Lipidated APOE-containing lipoprotein particles contain phospholipids and unesterified cholesterol in the shell, and esterified cholesterol and triglycerides form the core. APOE molecules are partially embedded in the phospholipid layer of the particles