Aß42-oligomer Interacting Peptide (AIP) neutralizes toxic amyloid-ß42 species and protects synaptic structure and function.
Sci Rep
; 5: 15410, 2015 Oct 29.
Article
em En
| MEDLINE
| ID: mdl-26510576
ABSTRACT
The amyloid-ß42 (Aß42) peptide is believed to be the main culprit in the pathogenesis of Alzheimer disease (AD), impairing synaptic function and initiating neuronal degeneration. Soluble Aß42 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 Aß-oligomer Interacting Peptide (AIP) that targets a relatively well-defined population of low-n Aß42 oligomers, rather than simply inhibiting the aggregation of Aß monomers into oligomers. Our data show that AIP diminishes the loss of Aß42-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 Aß42 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 Aß42-oligomer recognition and removal.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Oligopeptídeos
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Fragmentos de Peptídeos
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Sinapses
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Peptídeos beta-Amiloides
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Transmissão Sináptica
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Doença de Alzheimer
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Agregação Patológica de Proteínas
Limite:
Animals
Idioma:
En
Revista:
Sci Rep
Ano de publicação:
2015
Tipo de documento:
Article