title: Competitive Mirror Image Phage Display Derived Peptide Modulates Amyloid Beta Aggregation and Toxicity.
abstract: Alzheimer´s disease is the most prominent type of dementia and currently no causative treatment is available. According to recent studies, oligomeric species of the amyloid beta (Aβ) peptide appear to be the most toxic Aβ assemblies. Aβ monomers, however, may be not toxic per se and may even have a neuroprotective role. Here we describe a competitive mirror image phage display procedure that allowed us to identify preferentially Aβ1-42 monomer binding and thereby stabilizing peptides, which destabilize and thereby eliminate toxic oligomer species. One of the peptides, called Mosd1 (monomer specific d-peptide 1), was characterized in more detail. Mosd1 abolished oligomers from a mixture of Aβ1-42 species, reduced Aβ1-42 toxicity in cell culture, and restored the physiological phenotype in neuronal cells stably transfected with the gene coding for human amyloid precursor protein.
authors: Institute of Complex Systems, Structural Biochemistry (ICS-6), Research Centre Jülich, 52425 Jülich, Germany.
authors: Stephan
authors: S
authors: Rudolph
authors: Institute of Complex Systems, Structural Biochemistry (ICS-6), Research Centre Jülich, 52425 Jülich, Germany.
authors: Antonia Nicole
authors: AN
authors: Klein
authors: Institute of Complex Systems, Structural Biochemistry (ICS-6), Research Centre Jülich, 52425 Jülich, Germany.
authors: Markus
authors: M
authors: Tusche
authors: Institute of Complex Systems, Structural Biochemistry (ICS-6), Research Centre Jülich, 52425 Jülich, Germany.
authors: Christine
authors: C
authors: Schlosser
authors: Institute of Complex Systems, Structural Biochemistry (ICS-6), Research Centre Jülich, 52425 Jülich, Germany.
authors: Anne
authors: A
authors: Elfgen
authors: Institute of Complex Systems, Structural Biochemistry (ICS-6), Research Centre Jülich, 52425 Jülich, Germany.|Institut für Physikalische Biologie, Heinrich-Heine-Universität Düsseldorf, 40225 Düsseldorf, Germany.
authors: Oleksandr
authors: O
authors: Brener
authors: Neurochemistry Laboratory and Biobank, VU University Medical Center Amsterdam, The Netherlands.
authors: Charlotte
authors: C
authors: Teunissen
authors: Institute of Complex Systems, Structural Biochemistry (ICS-6), Research Centre Jülich, 52425 Jülich, Germany.|Institut für Physikalische Biologie, Heinrich-Heine-Universität Düsseldorf, 40225 Düsseldorf, Germany.
authors: Lothar
authors: L
authors: Gremer
authors: Institute of Complex Systems, Structural Biochemistry (ICS-6), Research Centre Jülich, 52425 Jülich, Germany.|Fakultät Angewandte Naturwissenschaften, Hochschule für angewandte Wissenschaften Coburg, 96450 Coburg, Germany.
authors: Susanne Aileen
authors: SA
authors: Funke
authors: Institute of Complex Systems, Structural Biochemistry (ICS-6), Research Centre Jülich, 52425 Jülich, Germany.
authors: Janine
authors: J
authors: Kutzsche
authors: Institute of Complex Systems, Structural Biochemistry (ICS-6), Research Centre Jülich, 52425 Jülich, Germany.|Institut für Physikalische Biologie, Heinrich-Heine-Universität Düsseldorf, 40225 Düsseldorf, Germany.
authors: Dieter
authors: D
authors: Willbold
mesh_terms: D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism* / Q000633:toxicity*; D002460:Cell Line; D061505:Cell Surface Display Techniques; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D010455:Peptides / Q000494:pharmacology*; D066329:Protein Aggregates / Q000187:drug effects*; D066263:Protein Aggregation, Pathological
chemical_list: D016229:Amyloid beta-Peptides; D010455:Peptides; D066329:Protein Aggregates; D053829:Amyloid Precursor Protein Secretases