This title appears in the Scientific Report :
2008
Please use the identifier:
http://hdl.handle.net/2128/25408 in citations.
Please use the identifier: http://dx.doi.org/10.1093/protein/gzm054 in citations.
Inhibition of cytotoxicity and amyloid fibril formation by a D-amino acid peptide that specifically binds to Alzheimer's disease amyloid peptide
Inhibition of cytotoxicity and amyloid fibril formation by a D-amino acid peptide that specifically binds to Alzheimer's disease amyloid peptide
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...
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Personal Name(s): | Wiesehan, K. |
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Stöhr, J. / Nagel-Steger, K. / van Groen, T. / Riesner, D. / Willbold, D. | |
Contributing Institute: |
Molekulare Biophysik; INB-2 |
Published in: | Protein engineering design and selection, 21 (2008) S. 241 - 246 |
Imprint: |
Oxford
Oxford Univ. Press
2008
|
Physical Description: |
241 - 246 |
DOI: |
10.1093/protein/gzm054 |
PubMed ID: |
18252750 |
Document Type: |
Journal Article |
Research Program: |
Funktion und Dysfunktion des Nervensystems |
Series Title: |
Protein Engineering Design & Selection
21 |
Subject (ZB): | |
Link: |
Get full text OpenAccess OpenAccess |
Publikationsportal JuSER |
Please use the identifier: http://dx.doi.org/10.1093/protein/gzm054 in citations.
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. |