title: Blood-brain barrier penetration of an Aβ-targeted, arginine-rich, d-enantiomeric peptide.
abstract: The application of small peptides targeting amyloid beta (Aβ) is one of many drug development strategies for the treatment of Alzheimer's disease (AD). We have previously identified several peptides consisting solely of D-enantiomeric amino acid residues obtained from mirror-image phage display selection, which bind to Aβ in different assembly states and eliminate toxic Aβ aggregates. Some of these D-peptides show both diagnostic and therapeutic potential in vitro and in vivo. Here we have analysed the similarity of the arginine-rich D-peptide D3 to the arginine-rich motif (ARM) of the human immunodeficiency virus type 1 transactivator of transcription (HIV-Tat) protein, and examined its in vivo blood-brain barrier (BBB) permeability using wild type mice and transgenic mouse models of Alzheimer's disease. We are able to demonstrate that D3 rapidly enters the brain where it can be found associated with amyloid plaques suggesting a direct penetration of BBB.
authors.affiliation: Forschungszentrum Jülich, Institute of Complex Systems, Structural Biochemistry, 52428 Jülich, Germany.
authors.forename: Nan
authors.initials: N
authors.lastname: Jiang
authors.affiliation: Forschungszentrum Jülich, Institute of Complex Systems, Structural Biochemistry, 52428 Jülich, Germany; European Molecular Biology Laboratory, Meyerhofstraße 1, 69117 Heidelberg, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Frenzel
authors.affiliation: Forschungszentrum Jülich, Institute of Complex Systems, Structural Biochemistry, 52428 Jülich, Germany.
authors.forename: Elena
authors.initials: E
authors.lastname: Schartmann
authors.affiliation: Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: van Groen
authors.affiliation: Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
authors.forename: Inga
authors.initials: I
authors.lastname: Kadish
authors.affiliation: Forschungszentrum Jülich, Institute of Neuroscience and Medicine, Medical Imaging Physics, 52428 Jülich, Germany.
authors.forename: N Jon
authors.initials: NJ
authors.lastname: Shah
authors.affiliation: Forschungszentrum Jülich, Institute of Neuroscience and Medicine, Medical Imaging Physics, 52428 Jülich, Germany; Department of Neurology, Faculty of Medicine, JARA, RWTH Aachen University, Aachen, Germany.
authors.forename: Karl-Josef
authors.initials: KJ
authors.lastname: Langen
authors.affiliation: Forschungszentrum Jülich, Institute of Complex Systems, Structural Biochemistry, 52428 Jülich, Germany; Heinrich-Heine-Universität Düsseldorf, Institut für Physikalische Biologie, 40225 Düsseldorf, Germany. Electronic address: D.Willbold@fz-juelich.de.
authors.forename: Dieter
authors.initials: D
authors.lastname: Willbold
authors.affiliation: Forschungszentrum Jülich, Institute of Neuroscience and Medicine, Medical Imaging Physics, 52428 Jülich, Germany. Electronic address: A.Willuweit@fz-juelich.de.
authors.forename: Antje
authors.initials: A
authors.lastname: Willuweit
mesh_terms: D000284:Administration, Oral; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000378:metabolism; D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002199:Capillary Permeability; D004195:Disease Models, Animal; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018696:Neuroprotective Agents / Q000138:chemical synthesis / Q000378:metabolism / Q000493:pharmacokinetics*; D009842:Oligopeptides / Q000138:chemical synthesis / Q000378:metabolism* / Q000493:pharmacokinetics; D016415:Sequence Alignment; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000737:chemistry
chemical_list: D016229:Amyloid beta-Peptides; C534952:D3 peptide; D018696:Neuroprotective Agents; D009842:Oligopeptides; D054322:tat Gene Products, Human Immunodeficiency Virus
keywords: Alzheimer's disease; Amyloid beta; Arginine-rich motif of HIV-Tat protein; Blood-brain barrier penetration; Transgenic mouse models; d-Enantiomeric peptide