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Involvement of the low-density lipoprotein receptor-related protein in the transcytosis of the brain delivery vector Angiopep-2
| Content Provider | Scilit |
|---|---|
| Author | Demeule, Michel Currie, Jean-Christophe Bertrand, Yanick Ché, Christian Nguyen, Tran Régina, Anthony Gabathuler, Reinhard Castaigne, Jean-Paul Béliveau, Richard |
| Copyright Year | 2008 |
| Description | Journal: Journal of Neurochemistry The blood-brain barrier (BBB) restricts the entry of proteins as well as potential drugs to cerebral tissues. We previously reported that a family of Kunitz domain-derived peptides called Angiopeps can be used as a drug delivery system for the brain. Here, we further characterize the transcytosis ability of these peptides using an in vitro model of the BBB and in situ brain perfusion. These peptides, and in particular Angiopep-2, exhibited higher transcytosis capacity and parenchymal accumulation than do transferrin, lactoferrin, and avidin. Angiopep-2 transport and accumulation in brain endothelial cells were unaffected by the P-glycoprotein inhibitor, cyclosporin A, indicating that this peptide is not a substrate for the efflux pump P-glycoprotein. However, competition studies show that activated alpha(2)-macroglobulin, a specific ligand for the low-density lipoprotein receptor-related protein-1 (LRP1) and Angiopep-2 can share the same receptor. In addition, LRP1 was detected in glioblastomas and brain metastases from lung and skin cancers. Fluorescent microscopy also revealed that Alexa488-Angiopep-2 co-localized with LRP1 in brain endothelial cell monolayers. Overall, these results suggest that Angiopep-2 transport across the BBB is, in part, mediated by LRP1. |
| Related Links | http://onlinelibrary.wiley.com/doi/10.1111/j.1471-4159.2008.05492.x/pdf |
| Ending Page | 1544 |
| Page Count | 11 |
| Starting Page | 1534 |
| e-ISSN | 14714159 |
| DOI | 10.1111/j.1471-4159.2008.05492.x |
| Journal | Journal of Neurochemistry |
| Issue Number | 4 |
| Volume Number | 106 |
| Language | English |
| Publisher | Wiley-Blackwell |
| Publisher Date | 2008-08-01 |
| Access Restriction | Open |
| Subject Keyword | Journal: Journal of Neurochemistry Biochemistry and Molecular Biology Blood–brain Barrier Low‐density Lipoprotein Receptor‐related Protein |
| Content Type | Text |
| Resource Type | Article |
