P-glycoprotein and breast cancer resistance protein restrict apical-to-basolateral permeability of human brain endothelium to amyloid-beta

J Cereb Blood Flow Metab. 2009 Jun;29(6):1079-83. doi: 10.1038/jcbfm.2009.42. Epub 2009 Apr 15.

Abstract

The clearance of amyloid beta (Abeta) from the brain represents a novel therapeutic target for Alzheimer's disease. Conflicting data exist regarding the contribution of adenosine triphosphate-binding cassette transporters to the clearance of Abeta through the blood-brain barrier. Therefore, we investigated whether Abeta could be a substrate for P-glycoprotein (P-gp) and/or for breast cancer resistance protein (BCRP) using a human brain endothelial cell line, hCMEC/D3. Inhibition of P-gp and BCRP increased apical-to-basolateral, but not basolateral-to-apical, permeability of hCMEC/D3 cells to (125)I Abeta 1-40. Our in vitro data suggest that P-gp and BCRP might act to prevent the blood-borne Abeta 1-40 from entering the brain.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism*
  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters / metabolism*
  • Amyloid beta-Peptides / metabolism*
  • Blood-Brain Barrier / metabolism*
  • Cell Line
  • Endothelium / metabolism
  • Humans
  • Neoplasm Proteins / metabolism*
  • Peptide Fragments / metabolism

Substances

  • ABCG2 protein, human
  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters
  • Amyloid beta-Peptides
  • Neoplasm Proteins
  • Peptide Fragments