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

被引：100

作者：

Tai, Leon M. ^{[1
]}

Loughlin, A. Jane ^{[1
]}

Male, David K. ^{[1
]}

Romero, Ignacio A. ^{[1
]}

机构：

[1] Open Univ, Dept Life Sci, Milton Keynes MK7 6AA, Bucks, England

来源：

JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM | 2009年 / 29卷 / 06期

基金：

英国医学研究理事会;

关键词：

Alzheimer's disease; amyloid beta; BCRP; blood-brain barrier; P-gp; DRUG EFFLUX TRANSPORTERS; BARRIER; CLEARANCE; LOCALIZATION; TRANSCYTOSIS; ENDOCYTOSIS; RECEPTORS; BINDING; CELLS; MODEL;

D O I：

10.1038/jcbfm.2009.42

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

The clearance of amyloid beta (A beta) 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 Ab through the blood-brain barrier. Therefore, we investigated whether Ab 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 I-125 A beta 1- 40. Our in vitro data suggest that P-gp and BCRP might act to prevent the blood-borne A beta 1- 40 from entering the brain. Journal of Cerebral Blood Flow & Metabolism (2009) 29, 1079-1083; doi:10.1038/jcbfm.2009.42; published online 15 April 2009

引用

页码：1079 / 1083

页数：5

共 16 条

[1] P-glycoprotein deficiency at the blood-brain barrier increases amyloid-β deposition in an Alzheimer disease mouse model [J].

Cirrito, JR ;

Deane, R ;

Fagan, AM ;

Spinner, ML ;

Parsadanian, M ;

Finn, MB ;

Jiang, H ;

Prior, JL ;

Sagare, A ;

Bales, KR ;

Paul, SM ;

Zlokovic, BV ;

Piwnica-Worms, D ;

Holtzman, DM .

JOURNAL OF CLINICAL INVESTIGATION, 2005, 115 (11) :3285-3290

[2] Localisation of breast cancer resistance protein in microvessel endothelium of human brain [J].

Cooray, HC ;

Blackmore, CG ;

Maskell, L ;

Barrand, MA .

NEUROREPORT, 2002, 13 (16) :2059-2063

[3] β-Amyloid-induced migration of monocytes across human brain endothelial cells involves RAGE and PECAM-1 [J].

Giri, R ;

Shen, YM ;

Stins, M ;

Yan, SD ;

Schmidt, AM ;

Stern, D ;

Kim, KS ;

Zlokovic, B ;

Kalra, VK .

AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY, 2000, 279 (06) :C1772-C1781

[4]

Hardy J, 2006, J ALZHEIMERS DIS, V9, P151

[5] Functional characterization of the brain-to-blood efflux clearance of human amyloid-β peptide (1-40) across the rat blood-brain barrier [J].

Ito, Shingo ;

Ohtsuki, Sumio ;

Terasaki, Tetsuya .

NEUROSCIENCE RESEARCH, 2006, 56 (03) :246-252

[6] MDR1-P-glycoprotein (ABCB1) mediates transport of Alzheimer's amyloid-β peptides -: Implications for the mechanisms of Aβ clearance at the blood-brain barrier [J].

Kuhnke, Diana ;

Jedlitschky, Gabriele ;

Grube, Markus ;

Krohn, Markus ;

Jucker, Mathias ;

Mosyagin, Igor ;

Cascorbi, Ingolf ;

Walker, Lary C. ;

Kroemer, Heyo K. ;

Warzok, Rolf W. ;

Vogelgesang, Silke .

BRAIN PATHOLOGY, 2007, 17 (04) :347-353

[7] β-Amyloid efflux mediated by p-glycoprotein [J].

Lam, FC ;

Liu, RH ;

Lu, PH ;

Shapiro, AB ;

Renoir, JM ;

Sharom, FJ ;

Reiner, PB .

JOURNAL OF NEUROCHEMISTRY, 2001, 76 (04) :1121-1128

[8] Antibody-based approaches in Alzheimer's research: safety, pharmacokinetics, metabolism, and analytical tools [J].

Lichtlen, Peter ;

Mohajeri, M. Hasan .

JOURNAL OF NEUROCHEMISTRY, 2008, 104 (04) :859-874

[9] Role of drug efflux transporters in the brain for drug disposition and treatment of brain diseases [J].

Löscher, W ;

Potschka, H .

PROGRESS IN NEUROBIOLOGY, 2005, 76 (01) :22-76

[10] Human blood-brain barrier receptors for Alzheimer's amyloid-β 1-40 -: Asymmetrical binding, endocytosis, and transcytosis at the apical side of brain microvascular endothelial cell monolayer [J].

Mackic, JB ;

Stins, M ;

McComb, JG ;

Calero, M ;

Ghiso, J ;

Kim, KS ;

Yan, SD ;

Stern, D ;

Schmidt, AM ;

Frangione, B ;

Zlokovic, BV .

JOURNAL OF CLINICAL INVESTIGATION, 1998, 102 (04) :734-743

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