| DOI | Resolve DOI: https://doi.org/10.1111/j.1582-4934.2009.00930.x |
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| Author | Search for: Bertrand, Yanick; Search for: Currie, Jean-Christophe; Search for: Demeule, Michel; Search for: Régina, Anthony; Search for: Ché, Christian; Search for: Abulrob, Abedelnasser1; Search for: Fatehi, Dorothy1; Search for: Sartelet, Hervé; Search for: Gabathuler, Reinhard; Search for: Castaigne, Jean-Paul; Search for: Stanimirovic, Danica1; Search for: Béliveau, Richard |
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| Affiliation | - National Research Council Canada. NRC Institute for Biological Sciences
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| Format | Text, Article |
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| Subject | blood-brain barrier; therapeutics; drug delivery; Angiopeps; low-density lipoprotein receptor-related protein-1; receptor-mediated transcytosis; brain disease |
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| Abstract | 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. |
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| Publication date | 2009-10-10 |
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| In | |
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| Language | English |
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| Peer reviewed | Yes |
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| NPARC number | 15336778 |
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| Export citation | Export as RIS |
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| Report a correction | Report a correction (opens in a new tab) |
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| Record identifier | 1029ec3d-7122-4a70-ad67-54d6072ebb9b |
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| Record created | 2010-05-21 |
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| Record modified | 2020-04-16 |
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