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First published online September 29, 2004

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Bridging the blood-brain barrier

The blood-brain barrier (BBB) stops most peptides entering the CNS and represents a significant obstacle to therapies for neurological disorders. Identifying carriers that could transport peptide-based drugs across the endothelial cells of the BBB is therefore an important goal but so far largely unattained. Weihong Pan and co-workers now reveal that a chaperone protein called RAP that normally facilitates folding and trafficking of low-density lipoprotein (LDL) receptors might be the answer (see p. 5071). Using ¹²⁵I-labelled RAP, they show that the chaperone efficiently crosses the BBB both in brain-perfusion assays and in vivo when injected intravenously. They then dissect the transport mechanism, demonstrating that passage of RAP across epithelial monolayers in vitro is promoted by megalin - a protein implicated in transcytosis across several types of epithelial cell. At 39 kDa, RAP is large enough to serve as a transporter for smaller molecules. Moreover, its transport across the BBB is significantly more efficient than that of two other potential carriers, transferrin and melanotransferrin. RAP thus has exciting potential as a vehicle for peptide-based drugs that target the CNS.

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Related articles in JCS:

Efficient transfer of receptor-associated protein (RAP) across the blood-brain barrier

Weihong Pan, Abba J. Kastin, Todd C. Zankel, Peter van Kerkhof, Tetsuya Terasaki, and Guojun Bu
JCS 2004 117: 5071-5078. [Abstract] [Full Text]  

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in JCS Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Search for Related Content Social Bookmarking                         What's this?