Home LiteratureArticle Details
PMID: 15717066 Published · ppublish English Journal Article Review

Blood-brain barrier genomics, proteomics, and new transporter discovery.

NeuroRx : the journal of the American Society for Experimental NeuroTherapeutics ·Vol. 2 ·No. 1 ·2005-01-00 ·Pages 151-61

Shusta EV

Abstract

The blood-brain barrier (BBB) is an impermeable cellular interface that physically separates the blood from the interstices of the brain. The endothelial cells lining the brain blood vessels form the principle barrier, and their unique phenotype is a consequence of dynamic interactions with several perivascular cell types present in the brain parenchyma. In addition, BBB dysfunction has been observed in the large majority of neurological diseases, but the causes of aberrant vascular behavior are generally unknown. Because of its barrier phenotype, drug delivery to the brain has also proven to be a very difficult task. Global genomics and proteomics analyses are currently being used to examine BBB function in healthy and diseased brain to better characterize this dynamic interface. It is becoming increasingly evident that these approaches have the potential to clarify the unique attributes of a healthy BBB, to identify therapeutic targets in diseased brain, and to identify novel conduits for noninvasive delivery of drugs against these targets. This review will discuss the application of genomics and proteomics to blood-brain barrier research and will offer views on the prospects of such approaches.

MeSH Terms
Animals Blood-Brain Barrier/physiology Carrier Proteins/metabolism Genomics Humans Nervous System Diseases/therapy Proteomics
Chemicals
Carrier Proteins
Authors & Affiliations
1 authors, click to expand affiliations / ORCID
Shusta Eric V
Department of Chemical and Biological Engineering, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA. shusta@engr.wisc.edu
References (48)
48 references, click to expand
  1. Gene microarray analysis of human brain arteriovenous malformations.
    Neurosurgery. 2004 Feb;54(2):410-23; discussion 423-5 PMID: 14744289
  2. The expression and functional characterization of ABCG2 in brain endothelial cells and vessels.
    FASEB J. 2003 Nov;17(14):2085-7 PMID: 12958161
  3. Culture of murine brain microvascular endothelial cells that maintain expression and cytoskeletal association of tight junction-associated proteins.
    In Vitro Cell Dev Biol Anim. 2003 Jul-Aug;39(7):313-20 PMID: 14613336
  4. Differentially expressed genes in hypertensive rats developing cerebral ischemia.
    Life Sci. 2004 Feb 27;74(15):1899-909 PMID: 14761671
  5. Putative endogenous mediators of preconditioning-induced ischemic tolerance in rat brain identified by genomic and proteomic analysis.
    J Neurochem. 2004 Apr;89(1):73-89 PMID: 15030391
  6. Congruence of tissue expression profiles from Gene Expression Atlas, SAGEmap and TissueInfo databases.
    BMC Genomics. 2003 Jul 29;4(1):31 PMID: 12885301
  7. Analysis of VEGF-responsive genes involved in the activation of endothelial cells.
    Mol Cancer. 2003 Jul 9;2:25 PMID: 12904264
  8. Altered ratios of measles virus transcripts in diseased human brains.
    Virology. 1987 Oct;160(2):523-6 PMID: 3660593
  9. A one-step procedure for isolation of poly(A)+ mRNA from isolated brain capillaries and endothelial cells in culture.
    J Neurochem. 1991 Dec;57(6):2136-9 PMID: 1940920
  10. Quantitative monitoring of gene expression patterns with a complementary DNA microarray.
    Science. 1995 Oct 20;270(5235):467-70 PMID: 7569999
  11. Serial analysis of gene expression.
    Science. 1995 Oct 20;270(5235):484-7 PMID: 7570003
  12. Suppression subtractive hybridization: a method for generating differentially regulated or tissue-specific cDNA probes and libraries.
    Proc Natl Acad Sci U S A. 1996 Jun 11;93(12):6025-30 PMID: 8650213
  13. A comparison of selected mRNA and protein abundances in human liver.
    Electrophoresis. 1997 Mar-Apr;18(3-4):533-7 PMID: 9150937
  14. A single amino acid change in the hemagglutinin protein of measles virus determines its ability to bind CD46 and reveals another receptor on marmoset B cells.
    J Virol. 1998 Apr;72(4):2905-16 PMID: 9525611
  15. CNS drug design based on principles of blood-brain barrier transport.
    J Neurochem. 1998 May;70(5):1781-92 PMID: 9572261
  16. Basal cell adhesion molecule/lutheran protein. The receptor critical for sickle cell adhesion to laminin.
    J Clin Invest. 1998 Jun 1;101(11):2550-8 PMID: 9616226
  17. SPARC (BM-40, osteonectin) inhibits the mitogenic effect of vascular endothelial growth factor on microvascular endothelial cells.
    J Biol Chem. 1998 Nov 6;273(45):29635-40 PMID: 9792673
  18. Critical factors in basal cell adhesion molecule/lutheran-mediated adhesion to laminin.
    J Biol Chem. 1999 Jan 8;274(2):728-34 PMID: 9873008
  19. Correlation between protein and mRNA abundance in yeast.
    Mol Cell Biol. 1999 Mar;19(3):1720-30 PMID: 10022859
  20. Endothelial claudin: claudin-5/TMVCF constitutes tight junction strands in endothelial cells.
    J Cell Biol. 1999 Oct 4;147(1):185-94 PMID: 10508865
  21. Arrest of G(1)-S progression by the p53-inducible gene PC3 is Rb dependent and relies on the inhibition of cyclin D1 transcription.
    Mol Cell Biol. 2000 Mar;20(5):1797-815 PMID: 10669755
  22. Membrane proteins and proteomics: un amour impossible?
    Electrophoresis. 2000 Apr;21(6):1054-70 PMID: 10786880
  23. Selective Lutheran glycoprotein gene expression at the blood-brain barrier in normal brain and in human brain tumors.
    J Cereb Blood Flow Metab. 2000 Jul;20(7):1096-102 PMID: 10908043
  24. The FXYD gene family of small ion transport regulators or channels: cDNA sequence, protein signature sequence, and expression.
    Genomics. 2000 Aug 15;68(1):41-56 PMID: 10950925
  25. In silico cloning of novel endothelial-specific genes.
    Genome Res. 2000 Nov;10(11):1796-806 PMID: 11076864
  26. Blood-brain barrier genomics.
    J Cereb Blood Flow Metab. 2001 Jan;21(1):61-8 PMID: 11149669
  27. The sequence of the human genome.
    Science. 2001 Feb 16;291(5507):1304-51 PMID: 11181995
  28. Initial sequencing and analysis of the human genome.
    Nature. 2001 Feb 15;409(6822):860-921 PMID: 11237011
  29. Altered gene expression in cerebral capillaries of stroke-prone spontaneously hypertensive rats.
    Brain Res. 2001 Aug 10;910(1-2):106-15 PMID: 11489260
  30. CNS involvement in primary Sjögren's syndrome: prevalence, clinical aspects, diagnostic assessment and therapeutic approach.
    CNS Drugs. 2001;15(8):597-607 PMID: 11524032
  31. Cell biology of caveolae and caveolin.
    Adv Drug Deliv Rev. 2001 Jul 28;49(3):223-35 PMID: 11551396
  32. Overexpression of multiple drug resistance genes in endothelial cells from patients with refractory epilepsy.
    Epilepsia. 2001 Dec;42(12):1501-6 PMID: 11879359
  33. Vascular genomics of the human brain.
    J Cereb Blood Flow Metab. 2002 Mar;22(3):245-52 PMID: 11891429
  34. A transmembrane tight junction protein selectively expressed on endothelial cells and platelets.
    J Biol Chem. 2002 May 3;277(18):16294-303 PMID: 11847224
  35. The central nervous system in systemic lupus erythematosus. Part 1. Clinical syndromes: a literature investigation.
    Rheumatology (Oxford). 2002 Jun;41(6):605-18 PMID: 12048286
  36. Vascular proteomics and subtractive antibody expression cloning.
    Mol Cell Proteomics. 2002 Jan;1(1):75-82 PMID: 12096143
  37. Subtractive expression cloning reveals high expression of CD46 at the blood-brain barrier.
    J Neuropathol Exp Neurol. 2002 Jul;61(7):597-604 PMID: 12125738
  38. Rat blood-brain barrier genomics. II.
    J Cereb Blood Flow Metab. 2002 Nov;22(11):1319-26 PMID: 12439289
  39. Overexpression of the EGFR/FKBP12/HIF-2alpha pathway identified in childhood astrocytomas by angiogenesis gene profiling.
    Cancer Res. 2003 Apr 15;63(8):1865-70 PMID: 12702575
  40. Size-selective loosening of the blood-brain barrier in claudin-5-deficient mice.
    J Cell Biol. 2003 May 12;161(3):653-60 PMID: 12743111
  41. Gene and protein expression profiling of human cerebral endothelial cells activated with tumor necrosis factor-alpha.
    Brain Res Mol Brain Res. 2003 Jul 23;115(2):130-46 PMID: 12877984
  42. Group B streptococcal beta-hemolysin/cytolysin activates neutrophil signaling pathways in brain endothelium and contributes to development of meningitis.
    J Clin Invest. 2003 Sep;112(5):736-44 PMID: 12952922
  43. DNA microarray profiling of developing PS1-deficient mouse brain reveals complex and coregulated expression changes.
    Mol Psychiatry. 2003 Oct;8(10):863-78 PMID: 14515137
  44. Gene expression profiling and functional proteomic analysis reveal perturbed kinase-mediated signaling in genetic stroke susceptibility.
    Physiol Genomics. 2003 Sep 29;15(1):75-83 PMID: 12902546
  45. The Ro52/SS-A autoantigen has elevated expression at the brain microvasculature.
    Neuroreport. 2003 Oct 6;14(14):1861-5 PMID: 14534436
  46. Functional characterization of rat brain-specific organic anion transporter (Oatp14) at the blood-brain barrier: high affinity transporter for thyroxine.
    J Biol Chem. 2003 Oct 31;278(44):43489-95 PMID: 12923172
  47. Classification of human astrocytic gliomas on the basis of gene expression: a correlated group of genes with angiogenic activity emerges as a strong predictor of subtypes.
    Cancer Res. 2003 Oct 15;63(20):6613-25 PMID: 14583454
  48. Endothelial cells co-cultured with wild-type and dominant/negative p53-transfected glioblastoma cells exhibit differential sensitivity to radiation-induced apoptosis.
    Int J Cancer. 2004 Mar 20;109(2):214-9 PMID: 14750172
Article Info
Journal
NeuroRx : the journal of the American Society for Experimental NeuroTherapeutics
Abbr.
NeuroRx
ISSN
1545-5343
DOI
10.1602/neurorx.2.1.151
Email
shusta@engr.wisc.edu
Published
2005-01-00
Pages
151-61
Language
English
Region
United States
NLM ID
101189456
PMCID
PMC539336
Subset
IM
External Links
PubMed source DOI: 10.1602/neurorx.2.1.151 PMC Full Text
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2