| DOI | Trouver le DOI : https://doi.org/10.1111/j.1582-4934.2009.00930.x |
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| Auteur | Rechercher : Bertrand, Yanick; Rechercher : Currie, Jean-Christophe; Rechercher : Demeule, Michel; Rechercher : Régina, Anthony; Rechercher : Ché, Christian; Rechercher : Abulrob, Abedelnasser1; Rechercher : Fatehi, Dorothy1; Rechercher : Sartelet, Hervé; Rechercher : Gabathuler, Reinhard; Rechercher : Castaigne, Jean-Paul; Rechercher : Stanimirovic, Danica1; Rechercher : Béliveau, Richard |
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| Affiliation | - Conseil national de recherches du Canada. Institut des sciences biologiques du CNRC
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| Format | Texte, Article |
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| Sujet | blood-brain barrier; therapeutics; drug delivery; Angiopeps; low-density lipoprotein receptor-related protein-1; receptor-mediated transcytosis; brain disease |
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| Résumé | 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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| Date de publication | 2009-10-10 |
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| Dans | |
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| Langue | anglais |
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| Publications évaluées par des pairs | Oui |
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| Numéro NPARC | 15336778 |
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| Exporter la notice | Exporter en format RIS |
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| Signaler une correction | Signaler une correction (s'ouvre dans un nouvel onglet) |
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| Identificateur de l’enregistrement | 1029ec3d-7122-4a70-ad67-54d6072ebb9b |
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| Enregistrement créé | 2010-05-21 |
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| Enregistrement modifié | 2020-04-16 |
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