Blood-brain barrier penetration of an Aβ-targeted, arginine-rich, D-enantiomeric peptide

Nan Jiang, Daniel Frenzel, Elena Schartmann, Thomas van Groen, Inga Kadish, N. Jon Shah, Karl Josef Langen, Dieter Willbold, Antje Willuweit

Research output: Contribution to journalArticleResearchpeer-review

15 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)2717-2724
Number of pages8
JournalBiochimica et Biophysica Acta - Biomembranes
Issue number11
Publication statusPublished - 1 Nov 2016
Externally publishedYes


  • Alzheimer's disease
  • Amyloid beta
  • Arginine-rich motif of HIV-Tat protein
  • Blood-brain barrier penetration
  • D-Enantiomeric peptide
  • Transgenic mouse models

Cite this