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Transport characteristics of a novel peptide platform for CNS therapeutics
| Content Provider | Scilit |
|---|---|
| Author | Bertrand, Yanick Currie, Jean-Christophe Demeule, Michel Régina, Anthony Ché, Christian Abulrob, Abedelnasser Fatehi, Dorothy Sartelet, Hervé Gabathuler, Reinhard Castaigne, Jean-Paul Stanimirovic, Danica Béliveau, Richard |
| Copyright Year | 2010 |
| Description | Journal: Journal of Cellular and Molecular Medicine New and effective therapeutics that cross the blood-brain barrier (BBB) are critically needed for treatment of many brain diseases. We characterize here a novel drug development platform that is broadly applicable for the development of new therapeutics with increased brain penetration. The platform is based on the Angiopep-2 peptide, a sequence derived from ligands that bind to low-density lipoprotein receptor-related protein-1 (LRP-1), a receptor expressed on the BBB. Fluorescent imaging studies of a Cy5.5Angiopep-2 conjugate and immunohistochemical studies of injected Angiopep-2 in mice demonstrated efficient transport across the BBB into brain parenchyma and subsequent co-localization with the neuronal nuclei-selective marker NeuN and the glial marker glial fibrillary acidic protein (GFAP). Uptake of [125I]-Angiopep-2 into brain endothelial cells occurred by a saturable mechanism involving LRP-1. The primary sequence and charge of Angiopep-2 were crucial for its passage across the BBB. Overall, the results demonstrate the significant potential of this platform for the development of novel neurotherapeutics. |
| Related Links | http://europepmc.org/articles/pmc3822732?pdf=render https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3822732/pdf http://onlinelibrary.wiley.com/doi/10.1111/j.1582-4934.2009.00930.x/pdf |
| Ending Page | 2839 |
| Page Count | 13 |
| Starting Page | 2827 |
| e-ISSN | 15824934 |
| DOI | 10.1111/j.1582-4934.2009.00930.x |
| Journal | Journal of Cellular and Molecular Medicine |
| Issue Number | 12 |
| Volume Number | 14 |
| Language | English |
| Publisher | Wiley-Blackwell |
| Publisher Date | 2010-12-01 |
| Access Restriction | Open |
| Subject Keyword | Journal: Journal of Cellular and Molecular Medicine Blood‐brain Barrier Low‐density Lipoprotein Receptor‐related Protein‐1 Receptor‐mediated Transcytosis |
| Content Type | Text |
| Resource Type | Article |
