Competitive Mirror Image Phage Display Derived Peptide Modulates Amyloid Beta Aggregation and Toxicity

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.

• Publication year

  2016

• Venue

  PLoS ONE

• Publication date

  2016-02-03

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1371/journal.pone.0147470PMID 26840229PMCID 4740492
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Blocking of the PD-1/PD-L1 Interaction by a D-Peptide Antagonist for Cancer Immunotherapy.

  2015cited by this paper
• QIAD assay for quantitating a compound’s efficacy in elimination of toxic Aβ oligomers

  2015cited by this paper
• Potential novel targets for Alzheimer pharmacotherapy: II. Update on secretase inhibitors and related approaches

  2014cited by this paper
• Structure-based study of antiamyloidogenic cyclic d,l-α-peptides

  2014cited by this paper
• Prion-like Mechanisms in Alzheimer's Disease.

  2014cited by this paper
• Amyloid-β(1–42) Protofibrils Formed in Modified Artificial Cerebrospinal Fluid Bind and Activate Microglia

  2013cited by this paper
• β-Amyloid oligomers in aging and Alzheimer’s disease

  2013cited by this paper
• Gamma secretase inhibitors of Notch signaling

  2013cited by this paper
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  2012cited by this paper
• Atomic force microscopy and MD simulations reveal pore-like structures of all-D-enantiomer of Alzheimer's β-amyloid peptide: relevance to the ion channel mechanism of AD pathology.

  2012cited by this paper
• Molecular Mimics of the Tumour Antigen MUC1

  2012cited by this paper
• Mirror image phage display--generating stable therapeutically and diagnostically active peptides with biotechnological means.

  2012cited by this paper
• Discovery of γ-secretase modulators with a novel activity profile by text-based virtual screening.

  2012cited by this paper
• Design, synthesis, and evaluation of resveratrol derivatives as Aß(₁-₄₂) aggregation inhibitors, antioxidants, and neuroprotective agents.

  2012cited by this paper
• Soluble Aβ oligomer production and toxicity

  2012cited by this paper
• A kinetic aggregation assay allowing selective and sensitive amyloid-β quantification in cells and tissues.

  2011cited by this paper
• Aβ Oligomer-Induced Synapse Degeneration in Alzheimer’s Disease

  2011cited by this paper
• Soluble amyloid β-protein dimers isolated from Alzheimer cortex directly induce Tau hyperphosphorylation and neuritic degeneration

  2011cited by this paper
• Alzheimer's disease.

  2010cited by this paper
• Size-dependent neurotoxicity of beta-amyloid oligomers.

  2010cited by this paper
• Development of a proteolytically stable retro-inverso peptide inhibitor of beta-amyloid oligomerization as a potential novel treatment for Alzheimer's disease.

  2010cited by this paper
• D-peptide inhibitors of the p53–MDM2 interaction for targeted molecular therapy of malignant neoplasms

  2010cited by this paper
• Oral treatment with the d-enantiomeric peptide D3 improves the pathology and behavior of Alzheimer's Disease transgenic mice.

  2010cited by this paper
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  2010cited by this paper
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  2010cited by this paper
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  2009cited by this paper
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  2009cited by this paper
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  2009cited by this paper
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  2008cited by this paper
• Amyloid-β protein dimers isolated directly from Alzheimer's brains impair synaptic plasticity and memory

  2008cited by this paper
• Amyloid-beta aggregation.

  2007cited by this paper
• Amyloid-β Aggregation

  2007cited by this paper
• Amyloid beta ion channel: 3D structure and relevance to amyloid channel paradigm.

  2007cited by this paper
• Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer's amyloid β-peptide

  2007cited by this paper
• Physiochemical characterization of the Alzheimer's disease‐related peptides Aβ1–42Arctic and Aβ1–42wt

  2006cited by this paper
• Physiochemical characterization of the Alzheimer's disease-related peptides A beta 1-42Arctic and A beta 1-42wt.

  2006cited by this paper
• Effects of secreted oligomers of amyloid β‐protein on hippocampal synaptic plasticity: a potent role for trimers

  2006cited by this paper
• Partial D-amino acid substitution: Improved enzymatic stability and preserved Ab recognition of a MUC2 epitope peptide.

  2005cited by this paper
• Prevention of Alzheimer's disease-associated Abeta aggregation by rationally designed nonpeptidic beta-sheet ligands.

  2004cited by this paper
• Prevention of Alzheimer's Disease-associated Aβ Aggregation by Rationally Designed Nonpeptidic β-Sheet Ligands*

  2004cited by this paper
• Mirror‐image Phage Display: Aiming at the Mirror

  2003cited by this paper
• The dementias.

  2002cited by this paper
• Phases of Aβ-deposition in the human brain and its relevance for the development of AD

  2002cited by this paper
• Fractionation and characterization of oligomeric, protofibrillar and fibrillar forms of beta-amyloid peptide.

  2000cited by this paper
• Translating cell biology into therapeutic advances in Alzheimer's disease

  1999cited by this paper
• Beta-sheet breaker peptide inhibitor of Alzheimer's amyloidogenesis with increased blood-brain barrier permeability and resistance to proteolytic degradation in plasma.

  1999cited by this paper
• Soluble pool of Aβ amyloid as a determinant of severity of neurodegeneration in Alzheimer's disease

  1999cited by this paper
• D-peptides as immunogens and diagnostic reagents.

  1998cited by this paper
• Diffusible, nonfibrillar ligands derived from Abeta1-42 are potent central nervous system neurotoxins.

  1998cited by this paper
• Different roles of D‐amino acids in immune phenomena

  1997cited by this paper
• Identification of d-Peptide Ligands Through Mirror-Image Phage Display

  1996cited by this paper
• [Clinical diagnosis and therapeutic possibilities for dementia of the Alzheimer type].

  1994cited by this paper
• Klinische Diagnostik und Therapiemöglichkeiten der Demenz vom Alzheimer-Typ

  1994cited by this paper
• Beta-amyloid precursor protein of Alzheimer disease occurs as 110- to 135-kilodalton membrane-associated proteins in neural and nonneural tissues.

  1988cited by this paper
• The precursor of Alzheimer's disease amyloid A4 protein resembles a cell-surface receptor

  1987cited by this paper
• Inhibition of (cid:1) -secretase causes increased secretion of amyloid precursor protein C-terminal fragments in association with exosomes

  year unknowncited by this paper

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