%0 Journal Article
%A Wiesehan, K.
%A Stöhr, J.
%A Nagel-Steger, K.
%A van Groen, T.
%A Riesner, D.
%A Willbold, D.
%T Inhibition of cytotoxicity and amyloid fibril formation by a D-amino acid peptide that specifically binds to Alzheimer's disease amyloid peptide
%J Protein engineering design and selection
%V 21
%@ 1741-0126
%C Oxford
%I Oxford Univ. Press
%M PreJuSER-338
%P 241 - 246
%D 2008
%Z Record converted from VDB: 12.11.2012
%X Alzheimer's disease (AD) is a progressive neurodegenerative disorder. The 'amyloid cascade hypothesis' assigns the amyloid-beta-peptide (Abeta) a central role in the pathogenesis of AD. Although it is not yet established, whether the resulting Abeta aggregates are the causative agent or just a result of the disease progression, polymerization of Abeta has been identified as a major feature during AD pathogenesis. Inhibition of the Abeta polymer formation, thus, has emerged as a potential therapeutic approach. In this context, we identified peptides consisting of d-enantiomeric amino acid peptides (d-peptides) that bind to Abeta. D-peptides are known to be more protease resistant and less immunogenic than the respective L-enantiomers. Previously, we have shown that a 12mer D-peptide specifically binds to Abeta amyloid plaques in brain tissue sections from former AD patients. In vitro obtained binding affinities to synthetic Abeta revealed a K(d) value in the submicromolar range. The aim of the present study was to investigate the influence of this d-peptide to Abeta polymerization and toxicity. Using cell toxicity assays, thioflavin fluorescence, fluorescence correlation spectroscopy and electron microscopy, we found a significant effect of the d-peptide on both. Presence of D-peptides (dpep) reduces the average size of Abeta aggregates, but increases their number. In addition, Abeta cytotoxicity on PC12 cells is reduced in the presence of dpep.
%K Amyloid beta-Peptides: antagonists & inhibitors
%K Amyloid beta-Peptides: metabolism
%K Amyloid beta-Peptides: toxicity
%K Animals
%K Cell Death: drug effects
%K Cytotoxins: antagonists & inhibitors
%K Cytotoxins: metabolism
%K Cytotoxins: toxicity
%K Microscopy, Electron
%K PC12 Cells
%K Peptides: chemistry
%K Peptides: metabolism
%K Peptides: pharmacology
%K Polymers: metabolism
%K Protein Binding
%K Protein Structure, Secondary: drug effects
%K Rats
%K Spectrometry, Fluorescence
%K Substrate Specificity
%K Thiazoles: metabolism
%K Amyloid beta-Peptides (NLM Chemicals)
%K Cytotoxins (NLM Chemicals)
%K Peptides (NLM Chemicals)
%K Polymers (NLM Chemicals)
%K Thiazoles (NLM Chemicals)
%K thioflavin T (NLM Chemicals)
%K J (WoSType)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:18252750
%U <Go to ISI:>//WOS:000254295200003
%R 10.1093/protein/gzm054
%U https://juser.fz-juelich.de/record/338