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Aβ42-oligomer Interacting Peptide (AIP) neutralizes toxic amyloid-β42 species and protects synaptic structure and function

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Item Type:Article
Title:Aβ42-oligomer Interacting Peptide (AIP) neutralizes toxic amyloid-β42 species and protects synaptic structure and function
Creators Name:Barucker, C. and Bittner, H.J. and Chang, P.K.Y. and Cameron, S. and Hancock, M.A. and Liebsch, F. and Hossain, S. and Harmeier, A. and Shaw, H. and Charron, F.M. and Gensler, M. and Dembny, P. and Zhuang, W. and Schmitz, D. and Rabe, J.P. and Rao, Y. and Lurz, R. and Hildebrand, P.W. and McKinney, R.A. and Multhaup, G.
Abstract:The amyloid-beta42 (Abeta42) peptide is believed to be the main culprit in the pathogenesis of Alzheimer disease (AD), impairing synaptic function and initiating neuronal degeneration. Soluble Abeta42 oligomers are highly toxic and contribute to progressive neuronal dysfunction, loss of synaptic spine density, and affect long-term potentiation (LTP). We have characterized a short, L-amino acid Abeta-oligomer Interacting Peptide (AIP) that targets a relatively well-defined population of low-n Abeta42 oligomers, rather than simply inhibiting the aggregation of Abeta monomers into oligomers. Our data show that AIP diminishes the loss of Abeta42-induced synaptic spine density and rescues LTP in organotypic hippocampal slice cultures. Notably, the AIP enantiomer (comprised of D-amino acids) attenuated the rough-eye phenotype in a transgenic Abeta42 fly model and significantly improved the function of photoreceptors of these flies in electroretinography tests. Overall, our results indicate that specifically "trapping" low-n oligomers provides a novel strategy for toxic Abeta42-oligomer recognition and removal.
Keywords:Alzheimer Disease, Amyloid {beta}-Peptides, Oligopeptides, Peptide Fragments, Pathological Protein Aggregation, Synapses, Synaptic Transmission, Animals, Drosophila Melanogaster, Mice, Rats
Source:Scientific Reports
ISSN:2045-2322
Publisher:Nature Publishing Group (U.K.)
Volume:5
Page Range:15410
Date:29 October 2015
Official Publication:https://doi.org/10.1038/srep15410
PubMed:View item in PubMed

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