P-glycoprotein and breast cancer resistance protein restrict apical-to-basolateral permeability of human brain endothelium to amyloid-beta.
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.
Department of Life Sciences, The Open University, Walton Hall, Milton Keynes, UK.
Leon M
LM
Tai
A Jane
AJ
Loughlin
David K
DK
Male
Ignacio A
IA
Romero
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D001812:Blood-Brain Barrier / Q000378:metabolism*; D002460:Cell Line; D004727:Endothelium / Q000378:metabolism; D006801:Humans; D009363:Neoplasm Proteins / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism
C116614:ABCG2 protein, human; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D016229:Amyloid beta-Peptides; D009363:Neoplasm Proteins; D010446:Peptide Fragments