Open AccessTransport characteristics of a novel peptide platform for CNS therapeutics
Author(s) -
Bertrand Yanick,
Currie JeanChristophe,
Demeule Michel,
Régina Anthony,
Ché Christian,
Abulrob Abedelnasser,
Fatehi Dorothy,
Sartelet Hervé,
Gabathuler Reinhard,
Castaigne JeanPaul,
Stanimirovic Danica,
Béliveau Richard
Publication year - 2010
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/j.1582-4934.2009.00930.x
Subject(s) - glial fibrillary acidic protein , blood–brain barrier , peptide , receptor , astrocyte , microbiology and biotechnology , biology , chemistry , cancer research , immunohistochemistry , neuroscience , central nervous system , biochemistry , immunology
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 [ 125 I]‐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.