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

被引:8
作者
Shusta E.V. [1 ,2 ]
机构
[1] Dept. of Chem. and Biol. Engineering, University of Wisconsin-Madison, Madison
[2] Dept. of Chem. and Biol. Engineering, University of Wisconsin-Madison, Madison, WI 53715
来源
NeuroRX | 2005年 / 2卷 / 1期
关键词
Suppression Subtractive Hybridization; Brain Endothelial Cell; Cereb Blood Flow; HUVEC Cell; Membrane Protein Expression;
D O I
10.1602/neurorx.2.1.151
中图分类号
学科分类号
摘要
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.
引用
收藏
页码:151 / 161
页数:10
相关论文
共 49 条
[1]  
Pardridge W.M., CNS drug design based on principles of blood-brain barrier transport, J Neurochem, 70, pp. 1781-1792, (1998)
[2]  
Boado R.J., Pardridge M.M., A one-step procedure for isolation of poly(A)+ mRNA from isolated brain capillaries and endothelial cells in culture, J Neurochem, 57, pp. 2136-2139, (1991)
[3]  
Shusta E.V., Boado R.J., Mathern G.W., Pardridge W.M., Vascular genomics of the human brain, J Cereb Blood Flow Metab, 22, pp. 245-252, (2002)
[4]  
Song L., Pachter J.S., Culture of murine brain microvascular endothelial cells that maintain expression and cytoskeletal association of tight junction-associated proteins, In Vitro Cell Dev Biol Anim, 39, pp. 313-320, (2003)
[5]  
Venter J.C., Adams M.D., Myers E.W., Li P.W., Mural R.J., Sutton G.G., Et al., The sequence of the human genome, Science, 291, pp. 1304-1351, (2001)
[6]  
Lander E.S., Linton L.M., Birren B., Nusbaum C., Zody M.C., Baldwin J., Et al., Initial sequencing and analysis of the human genome, Nature, 409, pp. 860-921, (2001)
[7]  
Schena M., Shalon D., Davis R.W., Brown P.O., Quantitative monitoring of gene expression patterns with a complementary DNA microarray, Science, 270, pp. 467-470, (1995)
[8]  
Diatchenko L., Lau Y.F., Campbell A.P., Chenchik A., Moqadam F., Huang B., Et al., Suppression subtractive hybridization: A method for generating differentially regulated or tissue-specific cDNA probes and libraries, Proc Natl Acad Sci USA, 93, pp. 6025-6030, (1996)
[9]  
Li J.Y., Boado R.J., Pardridge W.M., Blood-brain barrier genomics, J Cereb Blood Flow Metab, 21, pp. 61-68, (2001)
[10]  
Velculescu V.E., Zhang L., Vogelstein B., Kinzler K.W., Serial analysis of gene expression, Science, 270, pp. 484-487, (1995)