Restoring blood-brain barrier P-glycoprotein reduces brain amyloid-β in a mouse model of Alzheimer's disease

Molecular Pharmacology

Volumn 77, Issue 5, 2010, Pages 715-723

  Hartz, Anika M S ^a   Miller, David S ^b   Bauer, Björn ^c  

^a UNIVERSITY OF MINNESOTA MEDICAL SCHOOL   (United States)

^b NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES   (United States)

^c UNIVERSITY OF MINNESOTA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

16ALPHA CYANOPREGNENOLONE; AMYLOID BETA PROTEIN; CYCLOSPORIN A; GLYCOPROTEIN P; GLYCOPROTEIN P INHIBITOR; IVERMECTIN; PREGNANE X RECEPTOR; SODIUM CYANIDE; TARIQUIDAR; VALSPODAR; VERAPAMIL;

ACTIVE TRANSPORT; ALZHEIMER DISEASE; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; BLOOD BRAIN BARRIER; BRAIN CAPILLARY; CONFOCAL MICROSCOPY; CONTROLLED STUDY; DRUG EFFECT; ENZYME LINKED IMMUNOSORBENT ASSAY; IMMUNOHISTOCHEMISTRY; MALE; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; RECEPTOR UPREGULATION; TIGHT JUNCTION; TRANSGENIC MOUSE; WESTERN BLOTTING;

ACTINS; ALZHEIMER DISEASE; AMYLOID BETA-PROTEIN; AMYLOID BETA-PROTEIN PRECURSOR; ANIMALS; BIOLOGICAL TRANSPORT; BLOOD-BRAIN BARRIER; CAPILLARIES; CEREBROVASCULAR CIRCULATION; DISEASE MODELS, ANIMAL; HUMANS; MALE; MICE; MICE, TRANSGENIC; P-GLYCOPROTEIN; PEPTIDE FRAGMENTS; RECEPTORS, CELL SURFACE;

EID: 77951078680     PISSN: 0026895X     EISSN: 15210111     Source Type: Journal    
DOI: 10.1124/mol.109.061754     Document Type: Article

References (42)

1. Bauer B, Hartz AM, Fricker G, and Miller DS (2004) Pregnane X receptor up-regulation of P-glycoprotein expression and transport function at the blood-brain barrier. Mol Pharmacol 66:413-419. (Pubitemid 39329239)
2. Bauer B, Hartz AM, Lucking JR, Yang X, Pollack GM, and Miller DS (2008) Coordinated nuclear receptor regulation of the efflux transporter, Mrp2, and the phase-II metabolizing enzyme, GSTpi, at the blood-brain barrier. J Cereb Blood Flow Metab 28:1222-1234. (Pubitemid 351733346)
3. Bauer B, Yang X, Hartz AM, Olson ER, Zhao R, Kalvass JC, Pollack GM, and Miller DS (2006) In vivo activation of human pregnane X receptor tightens the blood-brain barrier to methadone through P-glycoprotein up-regulation. Mol Pharmacol 70:1212-1219. (Pubitemid 44435972)
4. Blennow K, de Leon MJ, and Zetterberg H (2006) Alzheimer's disease. Lancet 368:387-403.
5. Cirrito JR, Deane R, Fagan AM, Spinner ML, Parsadanian M, Finn MB, Jiang H, Prior JL, Sagare A, Bales KR, et al. (2005) P-glycoprotein deficiency at the blood-brain barrier increases amyloid-β deposition in an Alzheimer disease mouse model. J Clin Invest 115:3285-3290. (Pubitemid 41567593)
6. Dauchy S, Miller F, Couraud PO, Weaver RJ, Weksler B, Romero IA, Scherrmann JM, De Waziers I, and Declèves X (2009) Expression and transcriptional regulation of ABC transporters and cytochromes P450 in hCMEC/D3 human cerebral microvascular endothelial cells. Biochem Pharmacol 77:897-909.
7. Deane R, Du Yan S, Submamaryan RK, LaRue B, Jovanovic S, Hogg E, Welch D, Manness L, Lin C, Yu J, et al. (2003) RAGE mediates amyloid-β peptide transport across the blood-brain barrier and accumulation in brain. Nat Med 9:907-913. (Pubitemid 36889934)
8. Deane R, Wu Z, Sagare A, Davis J, Du Yan S, Hamm K, Xu F, Parisi M, LaRue B, Hu HW, et al. (2004a) LRP/amyloid β-peptide interaction mediates differential brain efflux of Aβ isoforms. Neuron 43:333-344. (Pubitemid 39061126)
9. Deane R, Wu Z, and Zlokovic BV (2004b) RAGE (yin) versus LRP (yang) balance regulates Alzheimer amyloid β-peptide clearance through transport across the blood-brain barrier. Stroke 35 (Suppl 1):2628-2631. (Pubitemid 39458354)
10. Donahue JE, Flaherty SL, Johanson CE, Duncan JA 3rd, Silverberg GD, Miller MC, Tavares R, Yang W, Wu Q, Sabo E, et al. (2006) RAGE, LRP-1, and amyloid-β protein in Alzheimer's disease. Acta Neuropathol 112:405-415. (Pubitemid 44469161)
11. Fellner S, Bauer B, Miller DS, Schaffrik M, Fankhänel M, Spruss T, Bernhardt G, Graeff C, Färber L, Gschaidmeier H, et al. (2002) Transport of paclitaxel (Taxol) across the blood-brain barrier in vitro and in vivo. J Clin Invest 110:1309-1318. (Pubitemid 35285757)
12. Geick A, Eichelbaum M, and Burk O (2001) Nuclear receptor response elements mediate induction of intestinal MDR1 by rifampin. J Biol Chem 276:14581-14587. (Pubitemid 37373327)
13. Greenberg SM, Gurol ME, Rosand J, and Smith EE (2004) Amyloid angiopathy-related vascular cognitive impairment. Stroke 35 (Suppl 1):2616-2619. (Pubitemid 39458351)
14. Hartz AM, Bauer B, Block ML, Hong JS, and Miller DS (2008) Diesel exhaust particles induce oxidative stress, proinflammatory signaling, and P-glycoprotein up-regulation at the blood-brain barrier. FASEB J 22:2723-2733.
15. Hartz AM, Bauer B, Fricker G, and Miller DS (2004) Rapid regulation of P-glycoprotein at the blood-brain barrier by endothelin-1. Mol Pharmacol 66:387-394. (Pubitemid 39329237)
16. Hooijmans CR, Graven C, Dederen PJ, Tanila H, van Groen T, and Kiliaan AJ (2007) Amyloid β deposition is related to decreased glucose transporter-1 levels and hippocampal atrophy in brains of aged APP/PS1 mice. Brain Res 1181:93-103. (Pubitemid 350050914)
17. Hsiao K, Chapman P, Nilsen S, Eckman C, Harigaya Y, Younkin S, Yang F, and Cole G (1996) Correlative memory deficits, Aβ elevation, and amyloid plaques in transgenic mice. Science 274:99-102. (Pubitemid 26332733)
18. Iadecola C (2004) Neurovascular regulation in the normal brain and in Alzheimer's disease. Nat Rev Neurosci 5:347-360. (Pubitemid 38568496)
19. Jones SA, Moore LB, Shenk JL, Wisely GB, Hamilton GA, McKee DD, Tomkinson NC, LeCluyse EL, Lambert MH, Willson TM, et al. (2000) The pregnane X receptor: a promiscuous xenobiotic receptor that has diverged during evolution. Mol Endocrinol 14:27-39.
20. Karlnoski RA, Rosenthal A, Kobayashi D, Pons J, Alamed J, Mercer M, Li Q, Gordon MN, Gottschall PE, and Morgan D (2009) Suppression of amyloid deposition leads to long-term reductions in Alzheimer's pathologies in Tg2576 mice. J Neurosci 29:4964-4971.
21. Kawarabayashi T, Younkin LH, Saido TC, Shoji M, Ashe KH, and Younkin SG (2001) Age-dependent changes in brain, CSF, and plasma amyloid β protein in the Tg2576 transgenic mouse model of Alzheimer's disease. J Neurosci 21:372-381. (Pubitemid 32107428)
22. King M, Su W, Chang A, Zuckerman A, and Pasternak GW (2001) Transport of opioids from the brain to the periphery by P-glycoprotein: peripheral actions of central drugs. Nat Neurosci 4:268-274. (Pubitemid 32194874)
23. Kliewer SA, Moore JT, Wade L, Staudinger JL, Watson MA, Jones SA, McKee DD, Oliver BB, Willson TM, Zetterström RH, et al. (1998) An orphan nuclear receptor activated by pregnanes defines a novel steroid signaling pathway. Cell 92:73-82. (Pubitemid 28053299)
24. Kuhnke D, Jedlitschky G, Grube M, Krohn M, Jucker M, Mosyagin I, Cascorbi I, Walker LC, Kroemer HK, Warzok RW, et al. (2007) MDR1-P-glycoprotein (ABCB1) mediates transport of Alzheimer's amyloid-β peptides: implications for the mechanisms of Aβ clearance at the blood-brain barrier. Brain Pathol 17:347-353. (Pubitemid 47537591)
25. Lam FC, Liu R, Lu P, Shapiro AB, Renoir JM, Sharom FJ, and Reiner PB (2001) β-Amyloid efflux mediated by p-glycoprotein. J Neurochem 76:1121-1128.
26. Lamba V, Yasuda K, Lamba JK, Assem M, Davila J, Strom S, and Schuetz EG (2004) PXR (NR1I2): splice variants in human tissues, including brain, and identification of neurosteroids and nicotine as PXR activators. Toxicol Appl Pharmacol 199:251-265. (Pubitemid 39208725)
27. Loeb MB, Molloy DW, Smieja M, Standish T, Goldsmith CH, Mahony J, Smith S, Borrie M, Decoteau E, Davidson W, et al. (2004) A randomized, controlled trial of doxycycline and rifampin for patients with Alzheimer's disease. J Am Geriatr Soc 52:381-387. (Pubitemid 38339518)
28. Mayer U, Wagenaar E, Dorobek B, Beijnen JH, Borst P, and Schinkel AH (1997) Full blockade of intestinal P-glycoprotein and extensive inhibition of blood-brain barrier P-glycoprotein by oral treatment of mice with PSC833. J Clin Invest 100:2430-2436. (Pubitemid 27514881)
29. Miller DS, Bauer B, and Hartz AM (2008) Modulation of P-glycoprotein at the blood-brain barrier: opportunities to improve central nervous system pharmacotherapy. Pharmacol Rev 60:196-209. (Pubitemid 351962009)
30. Mooradian AD, Chung HC, and Shah GN (1997) GLUT-1 expression in the cerebra of patients with Alzheimer's disease. Neurobiol Aging 18:469-474. (Pubitemid 27497142)
31. Pascussi JM, Drocourt L, Fabre JM, Maurel P, and Vilarem MJ (2000) Dexamethasone induces pregnane X receptor and retinoid X receptor-α expression in human hepatocytes: synergistic increase of CYP3A4 induction by pregnane X receptor activators. Mol Pharmacol 58:361-372. (Pubitemid 30497480)
32. Schinkel AH, Wagenaar E, Mol CA, and van Deemter L (1996) P-glycoprotein in the blood-brain barrier of mice influences the brain penetration and pharmacological activity of many drugs. J Clin Invest 97:2517-2524. (Pubitemid 26187339)
33. Shibata M, Yamada S, Kumar SR, Calero M, Bading J, Frangione B, Holtzman DM, Miller CA, Strickland DK, Ghiso J, et al. (2000) Clearance of Alzheimer's amyloid-ss(1-40) peptide from brain by LDL receptor-related protein-1 at the blood-brain barrier. J Clin Invest 106:1489-1499. (Pubitemid 32038587)
34. Tai LM, Loughlin AJ, Male DK, and Romero IA (2009) P-glycoprotein and breast cancer resistance protein restrict apical-to-basolateral permeability of human brain endothelium to amyloid-β. J Cereb Blood Flow Metab 29:1079-1083.
35. Vogelgesang S, Cascorbi I, Schroeder E, Pahnke J, Kroemer HK, Siegmund W, Kunert-Keil C, Walker LC, and Warzok RW (2002) Deposition of Alzheimer's β-amyloid is inversely correlated with P-glycoprotein expression in the brains of elderly nondemented humans. Pharmacogenetics 12:535-541. (Pubitemid 35177083)
36. Vogelgesang S, Warzok RW, Cascorbi I, Kunert-Keil C, Schroeder E, Kroemer HK, Siegmund W, Walker LC, and Pahnke J (2004) The role of P-glycoprotein in cerebral amyloid angiopathy; implications for the early pathogenesis of Alzheimer's disease. Curr Alzheimer Res 1:121-125.
37. Watkins RE, Wisely GB, Moore LB, Collins JL, Lambert MH, Williams SP, Willson TM, Kliewer SA, and Redinbo MR (2001) The human nuclear xenobiotic receptor PXR: structural determinants of directed promiscuity. Science 292:2329-2333.
38. Wenger RM (1986) Cyclosporine and analogues - isolation and synthesis - mechanism of action and structural requirements for pharmacological activity. Fortschr Chem Org Naturst 50:123-136.
39. Xiong H, Callaghan D, Jones A, Bai J, Rasquinha I, Smith C, Pei K, Walker D, Lue LF, Stanimirovic D, et al. (2009) ABCG2 is up-regulated in Alzheimer's brain with cerebral amyloid angiopathy and may act as a gatekeeper at the blood-brain barrier for Aβ(1-40) peptides. J Neurosci 29:5463-5475.
40. Zlokovic BV (2005) Neurovascular mechanisms of Alzheimer's neurodegeneration. Trends Neurosci 28:202-208.
41. Zlokovic BV (2008) The blood-brain barrier in health and chronic neurodegenerative disorders. Neuron 57:178-201.
42. Zlokovic BV and Frangione B (2003) Transport-clearance hypothesis for Alzheimer's disease and potential therapeutic implications, in Aβ Metabolism in Alzheimer's Disease (Saido TC ed) pp 114-122, Landes Bioscience, Georgetown, TX.