Figure 3.

Receptors and transporters on endothelial cells may be potential targets for therapies designed to promote Aβ clearance.

Upregulation of MEOX2 expression and downregulation of SRF/MYOCD expression can restore LRP1 levels and increase Aβ removal from the brain parenchyma. Upregulation of PICALM expression can increase Aβ-LRP1 complex endothelial transcytosis. Activation of PXR can upregulate the expression of P-gp, thereby promoting Aβ efflux from the brain. Activation of LXR can mediate upregulation of ABCA1, decreasing Aβ levels in the brain. Some tertiary amides block the interaction between RAGE and Aβ, precluding Aβ from reentering the brain. Downregulation of endothelial CCR5 expression can prevent the Aβ-RAGE complex from transmitting signals to the immune system. The blue line in the figure represents mediated Aβ outflow; the brown line represents mediated Aβ inflow; the green line represents activation or inhibition; solid lines represent receptors or transporters that directly mediate Aβ transport; dashed lines represent receptors or transporters that indirectly mediate Aβ transport. Aβ: Amyloid-beta; LRP1: low density lipoprotein receptor(LDLR)-related protein 1; LXR: Liver X Receptor; MEOX2: mesenchyme homeobox gene 2; MYOCD: myocardin; P-gp: P-glycoprotein; PICALM: phosphatidylinositol binding clathrin assembly protein; PXR: pregnane X receptor; RAGE: advanced glycation end products; SRF: serum response factor.