Prediction of Human Brain Penetration of P-glycoprotein and Breast Cancer Resistance Protein Substrates Using In Vitro Transporter Studies and Animal Models

2018 ◽  
Vol 107 (8) ◽  
pp. 2225-2235 ◽  
Author(s):  
Bo Feng ◽  
Angela C. Doran ◽  
Li Di ◽  
Mark A. West ◽  
Sarah M. Osgood ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Animal Models ◽  
Human Brain ◽  
Breast Cancer Resistance Protein ◽  
Cancer Resistance ◽  
Brain Penetration ◽  
Protein Substrates ◽  
P Glycoprotein ◽  
Resistance Protein

scholarly journals P-Glycoprotein and Breast Cancer Resistance Protein Restrict Apical-to-Basolateral Permeability of Human Brain Endothelium to Amyloid-β

2009 ◽  
Vol 29 (6) ◽  
pp. 1079-1083 ◽  
Author(s):  
Leon M Tai ◽  
A Jane Loughlin ◽  
David K Male ◽  
Ignacio A Romero
Keyword(s):  
Breast Cancer ◽  
Human Brain ◽  
Breast Cancer Resistance Protein ◽  
Amyloid Β ◽  
Cancer Resistance ◽  
Glycoprotein P ◽  
P Glycoprotein ◽  
Resistance Protein ◽  
The Brain

The clearance of amyloid beta (Aβ) from the brain represents a novel therapeutic target for Alzheimer's disease. Conflicting data exist regarding the contribution of adenosine triphosphatebinding cassette transporters to the clearance of Aβ through the blood-brain barrier. Therefore, we investigated whether Aβ 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 125l Aβ 1–40. Our in vitro data suggest that P-gp and BCRP might act to prevent the blood-borne Aβ 1–40 from entering the brain.

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