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Sci Rep. 2015 Oct 29;5:15410. doi: 10.1038/srep15410.

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

Author information

1
Department of Pharmacology and Therapeutics, Faculty of Medicine, McGill University, Montreal, QC, Canada.
2
Institute of Medical Physics and Biophysics, Charite-Universitätsmedizin, Germany.
3
Department of Neurology and Neurosurgery, Montreal, McGill Centre for Research in Neuroscience, Canada.
4
Institut für Chemie und Biochemie, Freie Universität Berlin, Germany.
5
Department of Physics &IRIS Adlershof, Humboldt-Universität zu Berlin, Germany.
6
Neurowissenschaftliches Forschungszentrum, Charite-Universitätsmedizin, German Center for Neurodegenerative Diseases (DZNE), Berlin, Germany.
7
Max-Planck-Institute for Molecular Genetics, Berlin, Germany.

Abstract

The amyloid-β42 (Aβ42) peptide is believed to be the main culprit in the pathogenesis of Alzheimer disease (AD), impairing synaptic function and initiating neuronal degeneration. Soluble Aβ42 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 Aβ-oligomer Interacting Peptide (AIP) that targets a relatively well-defined population of low-n Aβ42 oligomers, rather than simply inhibiting the aggregation of Aβ monomers into oligomers. Our data show that AIP diminishes the loss of Aβ42-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 Aβ42 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 Aβ42-oligomer recognition and removal.

PMID:
26510576
PMCID:
PMC4625140
DOI:
10.1038/srep15410
[Indexed for MEDLINE]
Free PMC Article

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