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@ARTICLE{Wiesehan:338,
author = {Wiesehan, K. and Stöhr, J. and Nagel-Steger, K. and van
Groen, T. and Riesner, D. and Willbold, D.},
title = {{I}nhibition of cytotoxicity and amyloid fibril formation
by a {D}-amino acid peptide that specifically binds to
{A}lzheimer's disease amyloid peptide},
journal = {Protein engineering design and selection},
volume = {21},
issn = {1741-0126},
address = {Oxford},
publisher = {Oxford Univ. Press},
reportid = {PreJuSER-338},
pages = {241 - 246},
year = {2008},
note = {Record converted from VDB: 12.11.2012},
abstract = {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.},
keywords = {Amyloid beta-Peptides: antagonists $\&$ inhibitors /
Amyloid beta-Peptides: metabolism / Amyloid beta-Peptides:
toxicity / Animals / Cell Death: drug effects / Cytotoxins:
antagonists $\&$ inhibitors / Cytotoxins: metabolism /
Cytotoxins: toxicity / Microscopy, Electron / PC12 Cells /
Peptides: chemistry / Peptides: metabolism / Peptides:
pharmacology / Polymers: metabolism / Protein Binding /
Protein Structure, Secondary: drug effects / Rats /
Spectrometry, Fluorescence / Substrate Specificity /
Thiazoles: metabolism / Amyloid beta-Peptides (NLM
Chemicals) / Cytotoxins (NLM Chemicals) / Peptides (NLM
Chemicals) / Polymers (NLM Chemicals) / Thiazoles (NLM
Chemicals) / thioflavin T (NLM Chemicals) / J (WoSType)},
cin = {INB-2},
ddc = {540},
cid = {I:(DE-Juel1)VDB805},
pnm = {Funktion und Dysfunktion des Nervensystems},
pid = {G:(DE-Juel1)FUEK409},
shelfmark = {Biochemistry $\&$ Molecular Biology / Biotechnology $\&$
Applied Microbiology},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:18252750},
UT = {WOS:000254295200003},
doi = {10.1093/protein/gzm054},
url = {https://juser.fz-juelich.de/record/338},
}